Keith Smolkowski (e-mail me)

NIDDM – Type 2 Diabetes

Oregon Research Institute

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Unit Conversions for Various Measures


Plasma Glucose 1 mmol/l = 18 mg/dl
Hemoglobin A1c 5% = 100 mg/dl or 5.6 mmol/l
6% = 135 mg/dl or 7.5 mmol/l
7% = 170 mg/dl or 9.4 mmol/l
Cholesterol 1 mmol/l = 39 mg/dl
Triglycerides 1 mmol/l = 89 mg/dl

Action to Control Cardiovascular Risk in Diabetes Study Group (2008). Effects of intensive glucose lowering in type 2 diabetes. New England Journal of Medicine, 358(24), 2545-2559.

For more information, see the Action to Control Cardiovascular Risk in Diabetes (ACCORD) web site at NHLBI.

Adolph, E. F. (1947). Urges to eat and drink in rats. American Journal of Physiology, 151, 110-125.

Atkinson, R. L., & Kaiser, D. L. (1985). Effects of calorie restriction and weight loss on glucose and insulin levels in obese humans. Journal of the American College of Nutrition. 4, 411-419. (Pub Med ID: 3900179)

One of several "studies of the low-carbohydrate diet [that] have shown that serum glucose and insulin levels decrease" (Yancy et al., 2004).

Baron, J. A., Schori, A., Crow, B., Carter, R., & Mann, J. I. (1986). A randomized controlled trial of low carbohydrate and low fat/high fiber diets for weight loss. American Journal of Public Health. 76(11), 1293-1296.

From the abstract: "We found that dieters given low carbohydrate/low fiber dietary advice tended to lose more weight than those given a higher carbohydrate/higher fiber regimen (5.0 vs 3.7 kg on average at three months). This pattern was particularly marked among women, and among participants who were under age 40 or of lower social class. . . . There were only minor differences in the serum lipoprotein patterns during the diet period. In view of these results, we believe previous claims of the benefits of fiber for weight loss may have been overstated. See also Foster et al. (2003), Gordon et al. (1963), Samaha et al. (2003), Shai et al. (2008), and Yancy et al. (2002).

Bass, J., & Takahashi, J. S. (2010, December 3). Circadian integration of metabolism and energetics. Science, 330(6009), 1349-1354. doi: 10.1126/science.1195027

Baumeister, R. F., Vohs, K. D., & Tice, D. M. (2007). The strength model of self-control. Current Directions In Psychological Science, 16(6), 351-355. doi: 10.1111/j.1467-8721.2007.00534.x

Discusses the role of blood glucose as an important component in self-control.

Benedict, C., Werner, K., Schmid, S. M., Schultes, B., Born, J., & Hallschmid, M. (2009). Early morning rise in hypothalamic-pituitary-adrenal activity: A role for maintaining the brain's energy balance. Psychoneuroendocrinology, 34(3), 455-462. doi: 10.1016/j.psyneuen.2008.10.010

Summary (Elsevier, 2009): "A profound rise in secretory activity in the early morning hours hallmarks the circadian regulation of the hypothalamic-pituitary-adrenal (HPA) stress axis. Functions and mechanisms underlying this regulation are barely understood. We tested the hypothesis that the early morning rise in HPA axis activity originates in part from a negative energy balance due to nocturnal fasting and concomitant increases in cerebral glucose demands. According to a 2×2 design, healthy men were infused with glucose (4.5mg/kgmin, 2300–0700h) and saline, respectively, during nocturnal sleep (n = 9) or wakefulness (n = 11). Circulating concentrations of ACTH, cortisol, glucose, insulin, and leptin were measured and food consumption in the next morning was assessed. Independent of sleep, glucose infusion reduced levels of ACTH (P < 0.01) and cortisol (P < 0.02) during the second night half. In the Sleep group, glucose infusion enhanced rapid eye movement (REM) sleep at the expense of sleep stage 2 (each P < 0.05). Glucose infusion increased leptin levels in both groups (P < 0.005) and reduced morning food intake in the Wake (P < 0.02) but not in the Sleep group (P > 0.46). Our findings support the view that increasing energy demands of the brain towards the end of the night essentially contribute to the early morning rise in HPA axis activity. Sleep is not critically involved in this glucose-glucocorticoid feedback loop but may reduce the brain's sensitivity to the anorexigenic effect of enhanced glucose supply."

Berne, C., & Björntorp, P. (2006). The metabolic syndrome. In B. B. Arnetz & R. Ekman (Eds.), Stress in health and disease (pp. 317-332). Weinheim, Germany: Wiley-VCH Veriag GmbH.

"This chapter examines the metabolic syndrome, also called insulin resistance syndrome, which denotes a group of risk factors for cardiovascular disease, among which insulin resistance is a key factor. The combination of abdominal obesity, with primarily intraabdominal (visceral) fat, and type 2 diabetes, impaired glucose tolerance or impaired fasting glucose, dyslipidemia characterized by high triglyceride levels and low high-density lipoprotein (HDL) cholesterol ("good cholesterol") and high blood pressure entails a significantly increased risk of developing or ultimately dying of cardiovascular disease. The metabolic syndrome implies a high probability of developing diabetes, which in turn significantly increases the risk of cardiovascular disease and microvascular diabetic complications in the eyes, kidneys and nervous system."

Bie, J., Bin, Z., Song, J., & Ghosh, S. (2010). Improved insulin sensitivity in high fat- and high cholesterol-fed ldlr-/- mice with macrophage-specific transgenic expression of cholesteryl ester hydrolase: Role of macrophage inflammation and infiltration into adipose tissue. Journal of Biological Chemistry, 285(18), 13630-13637.

See summary on ScienceDaily.

Björntorp, P. (1997). Body fat distribution, insulin resistance, and metabolic diseases. Nutrition, 13(9), 795-803. doi: 10.1016/S0899-9007(97)00191-3

Björntorp investigates the role of hypothalamic-pituitary-adrenal (HPA) axis function in obesity, insulin resistance, and metabolic diseases.

Björntorp, P. (1999). Neuroendocrine perturbations as a cause of insulin resistance. Diabetes/Metabolism Research And Reviews, 15(6), 427-441.

Bolen, S., Feldman, L., Vassy, J., Wilson, L., Yeh, H.-C., Marinopoulis, S., Wiley, C., Selvin, E., Wilson, R., Bass, E. B., & Brancati, F. L. (2007). Systematic review: Comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Annals of Internal Medicine, 147(6), 386-399.

"Conclusions: Compared with newer, more expensive agents (thiazolidinediones, α-glucosidase inhibitors, and meglitinides), older agents (second-generation sulfonylureas and metformin) have similar or superior effects on glycemic control, lipids, and other intermediate end points. Large, long-term comparative studies are needed to determine the comparative effects of oral diabetes agents on hard clinical end points" (p. 386, abstract).

Bonora, E., & Tuomilehto, J. (2011). The pros and cons of diagnosing diabetes with A1C. Diabetes Care, 34(S2), 5184-5190.

Boussageon, R., Bejan-Angoulvant, T., Saadatian-Elahi, M., Lafont, S., Bergeonneau, C., Kassaï, B., & ... Cornu, C. (2011). Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: Meta-analysis of randomised controlled trials. British Medical Journal, 343(7817), 244.

Boussageon et al. (2011) concluded that "the overall results of this meta-analysis show limited benefits of intensive glucose lowering treatment on all cause mortality and deaths from cardiovascular causes. We cannot exclude a 9% reduction or a 19% increase in all cause mortality and a 14% reduction or a 43% increase in cardiovascular death. The benefit:risk ratio of intensive glucose lowering treatment in the prevention of macrovascular and microvascular events remains uncertain. The harm associated with severe hypoglycaemia might counterbalance the potential benefit of intensive glucose lowering treatment" (abstract).

Chowdhury, R., Warnakula, S., Kunutsor, S., Crowe, F., Ward, H. A., Johnson, L., & ... Di Angelantonio, E. (2014). Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk. Annals of Internal Medicine, 160(6), 398-407. C&R

Chung, M., Balk, E. M., Ip, S., Raman, G., Yu, W. W., Trikalinos, T. A., Lichtenstein, A. H., Yetley, E. A., & Lau, J. (2009). Reporting of systematic reviews of micronutrients and health: A critical appraisal. American Journal of Clinical Nutrition 89, 1099-1113.

Dyer-Parziale, M. (2000). The effect of extend bar containing uncooked cornstarch on night-time glycemic excursion in suspects with type 2 diabetes. Diabetes Research and Clinical Practice 53(3), 137-139.

Eggleston, K. N., Shah, N. D., Smith, S. A., Wagie, A. E., Williams, A. R., Grossman, J. H., & . . . Newhouse, J. P. (2009). The Net Value of Health Care for Patients With Type 2 Diabetes, 1997 to 2005. Annals of Internal Medicine, 151(6), 386-W127.

Frost, C., & White, I. R. (2005). The effect of measurement error in risk factors that change over time in cohort studies: do simple methods overcorrect for 'regression dilution'? International Journal of Epidemiology, 34(6), 1359-1368. doi:10.1093/ije/dyi148

Foster, G. D., Wyatt, H. R., Hill, J. O., McGuckin, B. G., Brill, C., Mohammed, B. S., Szapary, P. O., Rader, D. J., Edman, J. S., & Klein, S. (2003). A randomized trial of a low-carbohydrate diet for obesity. New England Journal of Medicine, 348(21), 2082-2090.

From the abstract: "The low-carbohydrate diet produced a greater weight loss (absolute difference, approximately 4 percent) than did the conventional diet for the first six months, but the differences were not significant at one year. The low-carbohydrate diet was associated with a greater improvement in some risk factors for coronary heart disease." See also Baron et al. (1986), Gordon et al. (1963), Samaha et al. (2003), Shai et al. (2008), and Yancy et al. (2002).

Gailliot, M. T., Baumeister, R. F., DeWall, C., Maner, J. K., Plant, E., Tice, D. M., & ... Schmeichel, B. J. (2007). Self-control relies on glucose as a limited energy source: Willpower is more than a metaphor. Journal of Personality and Social Psychology, 92(2), 325-336.

Gordon, E. S. (1970). Metabolic aspects of obesity. Advances in Metabolic Disorders, 4, 229-296.

Greenfield, S., Billimek, J., Pellegrini, F., Franciosi, M., De Berardis, G., Nicolucci, A., & Kaplan, S. H. (2009). Comorbidity Affects the Relationship Between Glycemic Control and Cardiovascular Outcomes in Diabetes. Annals of Internal Medicine, 151(12), 854-W271.

Although this study has a number of important limitations, the authors concluded that "patients with the high levels of comorbidity common in type 2 diabetes may receive diminished cardiovascular benefit from intensive blood glucose control" (abstract). See also Montori and Fernández-Balsells (2009) and Kelly et al. (2009).

Halton, T. L., Liu, S., Manson, J. E., & Hu, F B. (2008). Low-carbohydrate-diet score and risk of type 2 diabetes in women. American Journal of Clinical Nutrition, 87(2), 339-346.

"These data suggest that diets lower in carbohydrate and higher in fat and protein do not increase the risk of type 2 diabetes in women. In fact, diets rich in vegetable sources of fat and protein may modestly reduce the risk of diabetes" (Abstract).

Holmäng, A., Mimura, K., Björntorp, P., & Lönnroth, P. (1997). Interstitial muscle insulin and glucose levels in normal and insulin-resistant Zucker rats. Diabetes, 46(11), 1799-1804.

From the abstract: "The data suggest that transport of insulin and glucose diffusion across the capillary wall are rate limiting for insulin as well as for glucose metabolism in muscle in normal rats. This does not appear to be the case in the insulin-resistant obese Zucker rats, where the reduced insulin responsiveness in muscle is due to muscular cellular defects rather than an inhibited transcapillary delivery of insulin."

Hyltoft Petersen, P., Lytken Larsen, M., & Hørder, M. (1987). Prerequisites for the maintenance of a certain state of health by biochemical monitoring. In E. K. Harris & T. Yasaka (eds.), Maintaining a healthy state within the individual (pp. 147-58). North-Holland: Elsevier.

See note for Phillipov and Phillips (2001).

Inzucchi, S. E., Bergenstal, R. M., Buse, J. B., Diamant, M., Ferrannini, E., Nauck, M., & ... Matthews, D. R. (2015). Management of hyperglycemia in Type 2 diabetes, 2015: A patient-centered approach: Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 38(1), 140-149. doi: 10.2337/dc14-2441

See comments at Diabetes Care by Mazzucchelli, Bordone, Maggi, and Cordera (2015), Landman, Kleefstra, and Houweling (2015), and McCormack, Martin, and Newman (2015). Inzucchi and Matthews (2015) and Herman (2015) offer a responses to comments.

Johannsson, G., Mårin, P., Lönn, L., Ottosson, M., Stenlöf, K., Björntorp, P., Sjöstroöm, L, & Bengtsson, B. A. (1997). Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure. Journal of Clinical Endocrinology and Metabolism, 82(3), 727-734.

From the abstract: "The most central findings in both GH deficiency in adults and the metabolic syndrome are abdominal/visceral obesity and insulin resistance. Abdominal obesity is associated with blunted GH secretion and low serum insulin-like growth factor-I concentrations. GH treatment in GH-deficient adults has demonstrated favorable effects on most of the features of GH deficiency in adults, but it is not known whether GH can improve some of the metabolic aberrations observed in abdominal/visceral obesity. . . . This trial has demonstrated that GH can favorably affect some of the multiple perturbations associated with abdominal/visceral obesity. This includes a reduction in abdominal/visceral obesity, an improved insulin sensitivity, and favorable effects on lipoprotein metabolism and diastolic blood pressure."

Kahn, R., & Fonseca, V. (2008). Translating the A1C assay. Diabetes Care, 31(8), 1704-1707.

Kaplan, N. M. (2001). Management of hypertension in patients with type 2 diabetes mellitus: Guidelines based on current evidence. Annals of Internal Medicine, 135, 1079-1083.

Kaufman, F.R., & Devgan, S. (1996). Use of uncooked cornstarch to avert nocturnal hypoglycemia in children and adolescents with type I diabetes. Journal of Diabetes Complications, 10, 84-87.

Kaufman, F. R,, Halvorson, M., & Kaufman, N. D. (1995). A randomized, blinded trial of uncooked cornstarch to diminish nocturnal hypoglycemia at Diabetes Camp. Diabetes Research and Clinical Practice, 30(3), 205-209.

Kaufman, F. R,, Halvorson, M., & Kaufman, N. D. (1997). Evaluation of a snack bar containing uncooked cornstarch in subjects with diabetes. Diabetes Research and Clinical Practice 35, 25-33.

Kelly, T. N., Bazzano, L. A., Fonseca, V. A., Thethi, T. K., Reynolds, K., & Jiang, H. (2009). Systematic Review: Glucose Control and Cardiovascular Disease in Type 2 Diabetes. Annals of Internal Medicine, 151(6), 394-W130.

From the abstract: "Intensive glucose control reduced the risk for some cardiovascular disease outcomes (such as nonfatal myocardial infarction), did not reduce the risk for cardiovascular death or all-cause mortality, and increased the risk for severe hypoglycemia." See also Montori and Fernández-Balsells (2009) and Greenfield et al. (2009).

Kim, E. K., Oh, T. J., Kim, L.-K., & Cho, Y. M. (2016). Improving effect of the acute administration of dietary fiber-enriched cereals on blood glucose levels and gut hormone secretion. Journal of Korean Medical Science, 31(2), 222-230. ¤

Kim, Oh, Kim, and Cho (2016) concluded that "acute administration of [dietary fiber-enriched cereal flakes] attenuates postprandial hyperglycemia without any significant change in the representative glucose-regulating hormones in patients with type 2 diabetes" (p. 222) when compared to conventional cereal flakes.

Kolatkar, N. S., Cembrowski, G. S., Callahan, P. L., Etzwiler, D. D. (1994). Intensive diabetes management requires very precise testing of glycohemoglobin [Letter]. Clinical Chemistry, 40, 1608-1610.

See note at Phillipov and Phillips (2001).

Kondo, T., Kishi, M., Fushimi, T., Ugajin, S., & Kaga, T. (2009). Vinegar intake reduces body weight, body fat mass, and serum triglyceride levels in obese Japanese subjects. Bioscience, Biotechnology, and Biochemistry, 73(8), 1837-1843.

Langfort, J., Pilis, W., Zarzeczny, R., Nazar, K., & Kaciuba-Uscilko H. (1996). Effect of low-carbohydrate-ketogenic diet on metabolic and hormonal responses to graded exercise in men. Journal of Physiological Pharmacology. 47, 361-371. (Pub Med ID: 8807563)

One of several "studies of the low-carbohydrate diet [that] have shown that serum glucose and insulin levels decrease" (Yancy et al., 2004).

Liatis, S., Grammatikou, S., Poulia, K.-A., Perrea, D., Makrilakis, K., Diakoumopoulou, E., & Katsilambros, N. (2010). Vinegar reduces postprandial hyperglycaemia in patients with type II diabetes when added to a high, but not to a low, glycaemic index meal. European Journal of Clinical Nutrition, 64, 727-732.

Lundgren, H., Bengtsson, C., Blohme, G., Isaakson, B., Lapidus, L., Lenner, R. A., Saaek, A., & Winther, E. (1989). Dietary habits and incidence of noninsulin-dependent diabetes melitus in a population study of women in Gothenburg, Sweden. American Journal of Clinical Nutrition, 49, 708-712.

Abstract: Dietary intake as initially estimated in a cross-sectional study has been related to the 12-y incidence of diabetes mellitus in a prospective study of 1462 women. In addition, all 50-y-old women (n = 352) were subjected to an intravenous glucose tolerance test. Because of the sampling procedure and a high participation rate the participants were representative of middle-aged women in the general population. No differences of statistical significance were observed concerning intake of energy and different nutrients. Neither did the number of meals nor the longest time between meals differ between women who developed diabetes and those who did not. Women with impaired glucose tolerance who developed diabetes did not differ from those who did not develop diabetes, concerning dietary intake. Body mass index was significantly higher in women who developed diabetes compared with other women. No specific dietary recommendations can be based on the results of this study.

Marshall, J. A., Hamman, R. F., & Baxter, J. (1991). High-fat, low-carbohydrate diet and the etiology of non-insulin-dependent diabetes mellitus: the San Luis Valley Diabetes Study. American Journal of Epidemiology, 134, 590-603.

Abstract: "Diet has long been believed to be an important risk factor for non-insulin-dependent diabetes. Animal studies generally support a relation between high-fat diets and development of insulin resistance. However, conclusive epidemiologic evidence is lacking. To further investigate the role of dietary fat and carbohydrate as potential risk factors for the onset of non-insulin-dependent diabetes mellitus, current diet was assessed among a geographically based group of 1,317 subjects without a prior diagnosis of diabetes who were seen in the period from 1984 to 1988 in two counties in southern Colorado. In this study, 24-hour diet recalls were reported prior to an oral glucose tolerance test. Persons with previously undiagnosed diabetes (n = 70) and impaired glucose tolerance (n = 171) were each compared with confirmed normal controls (n = 1,076). The adjusted odds ratios relating a 40-g/day increase in fat intake to non-insulin-dependent diabetes mellitus and impaired glucose tolerance were 1.51 (95% confidence interval 0.85–2.67) and 1.62 (95% confidence interval 1.09–2.41), respectively. Restricting cases to diabetic persons with fasting glucose >140 mg/dl and persons with impaired glucose tolerance confirmed on follow-up, the odds ratios increased to 3.03 (95% confidence interval 1.07–8.62) and 2.67 (95% confidence interval 1.33–5.36), respectively. The findings support the hypothesis that high-fat, low-carbohydrate diets are associated with the onset of non-insulin-dependent diabetes mellitus in humans."

This cross-sectional study provides only a correlation between fat intake and NIDDM—in this case an odds ratio, the correlational equivalent for dichotomous data—which one cannot interpret as causative. Why does this matter? In the 1940's, Curt Richter and Edward Adolph demonstrated that diabetic rats, which admittedly differ in important ways from humans, will curtail their carbohydrate intake (Adolph, 1947; Richter, 1976). Obviously rats know nothing about diabetes, yet diabetic rats will consume only fat and protein (Taubes, 2007). If humans behave, even to a small degree, like rats, one would then expect diabetic participants in this study to increase fat intake as a result of diabetes, not because it causes NIDDM. Richter demonstrated similar changes in dietary choice in rats due to impairment of the retention of salt and calcium (Taubes).

McCormack, J., & Greenhalgh, T. (2000). Seeing what you want to see in randomised controlled trials: versions and perversions of UKPDS data. British Medical Journal, 320(7251), 1720-1723. doi: 10.1136/bmj.320.7251.1720

From the abstract: When the UK prospective diabetes study (UKPDS) was published in 1998, many scientists stated that good blood sugar control could reduce the risk of diabetic complications. McCormack and Greenhalgh argue, however, that close attention to the study data show that insulin and oral sulphonylurea drugs had no effect on diabetic complications even though they lowered blood sugar.

McGarry, J. D. (1992, October 30). What if Minkowski had been ageusic? An alternative angle on diabetes. Science, 258(5083), 766-770.

Abstract: Despite decades of intensive investigation, the basic pathophysiological mechanisms responsible for the metabolic derangements associated with diabetes mellitus have remained elusive. Explored here is the possibility that traditional concepts in this area might have carried the wrong emphasis. It is suggested that the phenomena of insulin resistance and hyperglycemia might be more readily understood if viewed in the context of underlying abnormalities of lipid metabolism.

Meyer, K. A., Kushi, L. H., Jacobs, D. R., Jr, Slavin, J., Sellers, T. A., & Folsom, A. R. (2000). Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. American Journal of Clinical Nutrition, 71: 921-930.

This study adds to the growing body of inconsistent results provided by epidemiologic research into the relationship between carbohydrates and diabetes risk. "Errors in the measurement of dietary intake, diabetes incidences, and the covariates in this study" (p. 929) may contribute the the inconsistent results, as well as changes in the foods eaten by people with high blood sugar. See the note about Marshall, Hamman, and Baxter (1991). Regardless, the conclusions from this correlational study cannot be taken as anything more than descriptive and certainly do not allow for causal inferences (Morgan & Winship, 2007).

Montori, V. M., Fernández-Balsells, M. (2009). Glycemic control in type 2 diabetes: Time for an evidence-based about-face? Annals of Internal Medicine, 150(11), 803-808.

Interesting perspective piece revealing the generally unacknowledged problems with tight clycemic control in patients with NIDDM. Monti and Fernández-Balsells show that while the benefits are minimal, the risks of tight control are high and potentially include increased mortality (e.g., Action to Control Cardiovascular Risk in Diabetes Study Group, 2008; National Heart Lung and Blood Institute, 2008, February 6).

Mozaffarian, D., & Ludwig, D. S. (2015). The 2015 US dietary guidelines: Lifting the ban on total dietary fat. Journal of the American Medical Association, 313(24), 2421-2422.

Nathan, D. M., Kuenen, J., Borg, R., Zheng, H., Schoenfeld, D., Heine, R. J., & the A1c-Derived Average Glucose (ADAG) Study Group (2008). Translating the A1C assay into estimated average glucose values. Diabetes Care, 31, 1473-1479.

"The results clearly support the hypothesis that there is a strong linear relationship between mean blood glucose and A1C, with a coefficient of correlation (R2) of 0.84" (Kahn & Fonseca, 2008, p. ).

Nathan, D. M., Turgeon, H., & Regan, S. (2007). Relationship between glycated haemoglobin levels and mean glucose levels over time. Diabetologia, 50(11), 2239-44.

From the abstract: "The HbA(1c) results at weeks 8 and 12 correlated strongly (r = 0.90) with the CGM results during the preceding 8 and 12 weeks. A curvilinear (exponential) relationship and a linear regression captured the relationship with similarly high correlations, which allowed transformation of HbA(1c) values to a calculated mean glucose level."

National Heart Lung and Blood Institute. (2008, February 6). NHLBI changes intensive blood sugar treatment strategy in ACCORD clinical trial [News Conference Transcript]. Retrieved from NHLBI, Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial:

"ACCORD investigators found that among those adults with Type 2 diabetes, who are at especially high risk of cardiovascular disease, a medical treatment strategy to intensively lower their blood sugar levels below the current guidelines, increase [sic] the risk of death compared to standard blood sugar lowering treatment" (p. 3). See the article by the Action to Control Cardiovascular Risk in Diabetes Study Group in NEJM (above).

Nestle, M. (2007, September). Eating made simple. Scientific American, 296(3), 60-69.

Nestle begins her article with the assumption that the "basic dietary principles are not in dispute: eat less; move more; eat fruits, vegetables and whole grains; and avoid too much junk food." Unfortunately, these basic principles are in dispute and have been for some time. Friedman and Stricker (1976), Greenwood (1985), Le Magnen (1984), Pomerleau, Imbeault, Parker, & Doucet (2004), and Toates and Booth (1974) all raise questions about the assumption that one can simply eat less and exercise more to lose weight. See also Taubes (2007) for a lengthy review of the literature.

Nield, L., Summerbell, C. D., Hooper, L., Whittaker, V., & Moore, H. (2008). Dietary advice for the prevention of type 2 diabetes mellitus in adults. Cochrane Database of Systematic Reviews, 4. doi: 10.1002/14651858.CD005102.pub2

From The Cochrane Library abstract: "Authors' conclusions: There are no high quality data on the efficacy of dietary intervention for the prevention of type 2 diabetes. More well-designed, long-term studies, providing well-reported, high-quality data are required before proper conclusions can be made into the best dietary advice for the prevention of diabetes mellitus in adults."

Östman, E. Granfeldt, Y., Persson, L., & Björk, I. (2005). Vinegar supplementation lowers glucose and insulin responses and increases satiety after a bread meal in healthy subjects. European Journal of Clinical Nutrition, 59, 983-988.

Phillipov, G., & Phillips, P. J. (2001). Components of total measurement error for hemoglobin A1c determination. Clinical Chemistry, 47(10), 1851-1853. Retrieved from

Phillipov and Phillips show confidence bounds for A1c determination, such as ± 0.94 at 95% and ± 0.61 at 80% for a single specimen. "Accordingly . . . to be 80% confident that the ADA goal of < 7.0% has been achieved (single specimen), the measured HbA1c concentration should be < 6.4%" (p. 1852). Reliability improves with a second specimen. Hyltoft Petersen et al. (1987) found similar values. Kolatar et al. (1994) found smaller bounds, but they included patients with lower A1c values, on average, than Pillipov and Phillips and Hyltoft Petersen et al.

Phinney, S. D., Bistrian, B. R., Wolfe, R. R., & Blackburn, G. L. (1983). The human metabolic response to chronic ketosis without caloric restriction: Physical and biochemical adaptation. Metabolism. 32, 757-768. (Pub Med ID: 6865775)

One of several "studies of the low-carbohydrate diet [that] have shown that serum glucose and insulin levels decrease" (Yancy et al., 2004).

Ray, K. K., Seshasai, S. R. K., Wijesuriya, S., Sivakumaran, R., Nethercott, S., Preiss, D., Erquo, S., & Sattar, N. (2009). Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: A meta-analysis of randomised controlled trials. Lancet, 373(9677), 1765-1772.

The conclusion from the abstract: "Overall, intensive compared with standard glycemic control significantly reduces coronary events without an increased risk of death. However, the optimum mechanism, speed, and extent of HbA1c reduction might be different in differing populations." Conclusion by Szwarc (2009, May 31), and the actual data: the risks of intensive control of blood sugars for type 2 diabetes outweigh the benefits. See, for example, Montori and Fernández-Balsells (2009).

Romero-Corral, A., Montori, V. M., Somers, V. K., Korinek, J., Thomas, R. J., Allison, T. G., Mookadam, F., & Lopez-Jimenez, F. (2006). Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: A systematic review of cohort studies. Lancet, 368(9536), 666-678. doi:10.1016/S0140-6736(06)69251-9.

This paper demonstrates a lower risk of mortality associated with overweight and obesity than often cited. The authors blame the measure as unreliable, yet it may be that body weight, however defined, is not as indicative of overall health as many think, except perhaps in the extremes.

Rosmond, R., & Björntorp, P. (1998). Blood pressure in relation to obesity, insulin and the hypothalamic-pituitary-adrenal axis in Swedish men. Journal of Hypertension, 16(12 Pt 1), 1721-1726.

From the abstract: "CONCLUSIONS: These findings suggest that general and central obesity is independently related to blood pressure, and that insulin may account for only part of this association. The activity of the hypothalamic-pituitary-adrenal axis is apparently important for blood pressure regulation, suggesting that mechanisms of the central nervous system have an impact."

Rosmond, R., & Björntorp, P. (2000). The hypothalamic-pituitary-adrenal axis activity as a predictor of cardiovascular disease, type 2 diabetes and stroke. Journal of Internal Medicine, 247(2), 188-197. doi: 10.1046/j.1365-2796.2000.00603.x

Rosmond, R., Chagnon, M., Bouchard, C., & Björntorp, P. (2003). Increased abdominal obesity, insulin and glucose levels in nondiabetic subjects with a T29C polymorphism of the transforming growth factor-1 gene. Hormone Research, 59(4), 191-194. doi: 10.1159/000069323

Rosmond, R., Dallman, M. F., & Björntorp, P. (1998). Stress-related cortisol secretion in men: Relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities, Journal of Clinical Endocrinology and Metabolism, 83(6), 1853-1859.

Rosmond, R., Wallerius, S., Wanger, P., Martin, L., Holm, C., & Björntorp, P. (2003). A 5-year follow-up study of disease incidence in men with an abnormal hormone pattern. Journal of Internal Medicine, 254(4), 386. doi: 10.1046/j.1365-2796.2003.01205.x.

From the abstract: "These data suggest that an abnormal neuroendocrine secretory pattern is prospectively associated with an increased incidence of cardiovascular-related events and type 2 diabetes."

Salmeron, J., Ascherio, A., Rimm, E. B., Colditz, G. A., Spiegelman, D., Jenkins, D. J., Stampfer, M. J., Wing, A. L., & Willett, W. C. (1997). Dietary fiber, glycemic load, and risk of NIDDM in men. Diabetes Care, 20, 545-550.

Abstract: OBJECTIVE: Intake of carbohydrates that provide a large glycemic response has been hypothesized to increase the risk of NIDDM, whereas dietary fiber is suspected to reduce incidence. These hypotheses have not been evaluated prospectively. RESEARCH DESIGN AND METHODS: We examined the relationship between diet and risk of NIDDM in a cohort of 42,759 men without NIDDM or cardiovascular disease, who were 40-75 years of age in 1986. Diet was assessed at baseline by a validated semiquantitative food frequency questionnaire. During 6-years of follow-up, 523 incident cases of NIDDM were documented. RESULTS: The dietary glycemic index (an indicator of carbohydrate's ability to raise blood glucose levels) was positively associated with risk of NIDDM after adjustment for age, BMI, smoking, physical activity, family history of diabetes, alcohol consumption, cereal fiber, and total energy intake. Comparing the highest and lowest quintiles, the relative risk (RR) of NIDDM was 1.37 (95% CI, 1.02-1.83, P trend = 0.03). Cereal fiber was inversely associated with risk of NIDDM (RR = 0.70; 95% CI, 0.51-0.96, P trend = 0.007; for > 8.1 g/day vs. < 3.2 g/day). The combination of a high glycemic load and a low cereal fiber intake further increased the risk of NIDDM (RR = 2.17, 95% CI, 1.04-4.54) when compared with a low glycemic load and high cereal fiber intake. CONCLUSIONS: These findings support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of NIDDM in men. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of NIDDM.

Salmeron, J., Manson, J. E., Stampfer, M. J., Colditz, G. A., Wing, A. L., & Willett, W. C. (1997). Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women. Journal of the American Medical Association, 277, 472-477.

Abstract: OBJECTIVE: To examine prospectively the relationship between glycemic diets, low fiber intake, and risk of non-insulin-dependent diabetes mellitus. DESIGN: Cohort study. SETTING: In 1986, a total of 65173 US women 40 to 65 years of age and free from diagnosed cardiovascular disease, cancer, and diabetes completed a detailed dietary questionnaire from which we calculated usual intake of total and specific sources of dietary fiber, dietary glycemic index, and glycemic load. MAIN OUTCOME MEASURE: Non-insulin-dependent diabetes mellitus. RESULTS: During 6 years of follow-up, 915 incident cases of diabetes were documented. The dietary glycemic index was positively associated with risk of diabetes after adjustment for age, body mass index, smoking, physical activity, family history of diabetes, alcohol and cereal fiber intake, and total energy intake. Comparing the highest with the lowest quintile, the relative risk (RR) of diabetes was 1.37 (95% confidence interval [CI], 1.09-1.71, P trend=.005). The glycemic load (an indicator of a global dietary insulin demand) was also positively associated with diabetes (RR= 1.47; 95% CI, 1.16-1.86, P trend=.003). Cereal fiber intake was inversely associated with risk of diabetes when comparing the extreme quintiles (RR=0.72, 95% CI, 0.58-0.90, P trend=.001). The combination of a high glycemic load and a low cereal fiber intake further increased the risk of diabetes (RR=2.50, 95% CI, 1.14-5.51) when compared with a low glycemic load and high cereal fiber intake. CONCLUSIONS: Our results support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of diabetes in women. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of diabetes.

Samaha, F. F., Iqbal, N., Seshadri, P., Chicano, K. L., Daily, D. A., McGrory, J., Williams, T., Williams, M., Gracely, E. J., & Stern, L. (2003). A low-carbohydrate as compared with a low-fat diet in severe obesity. New England Journal of Medicine, 348(21), 2074-2081.

From the abstract: "Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet, with a relative improvement in insulin sensitivity and triglyceride levels, even after adjustment for the amount of weight lost." See also Baron et al. (1986), Foster et al. (2003), Gordon et al. (1963), Seshadri et al. (2004), Shai et al. (2008), and Yancy et al. (2002).

Stanhope, K., Schwarz, J., Keim, N., Griffen, S., Bremer, A., Graham, J., et al. (2009). Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. Journal of Clinical Investigation, 119(5), 1322-1334. doi:10.1172/JCI37385

Reports the likelihood that fructose (e.g., corn syrup), but not sucrose (sugar), leads to childhood obesity and diabetes.

Sherman, W. M., Katz, A. L., Cutler, C. L., Withers, R. T., & Ivy, J. L. (1988). Glucose transport: Locus of muscle insulin resistance in obese Zucker rats. American Journal of Physiology, Endocrinology and Metabolism, 255(3), E374-E382.

Shermer, M. (2007, February). Skeptic: Eat, drink and be merry: Or why we should learn to stop worrying and love food. Scientific American, 29.

Sims, E. A. H., Danforth Jr, E., Horton, E. S., Bray, G. A., Glennon, J. A., & Salans, L. B. (1973). Endocrine and metabolic effects of experimental obesity in man. Recent Progress In Hormone Research, 29, 457-496.

Demonstrated that over-consumption of food was not the cause for the genesis of obesity. Most volunteers maintained a fairly stable weight, despite incredibly excessive food intake (e.g., 7000 callories per day; see also Taubes, 2007, p. 272-273).

Siri-Tarino, P. W., Sun, Q., Hu, F. B., & Krauss, R. M. (2010). Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. American Journal of Clinical Nutrition, 91(3), 535-546. doi: 10.3945/ajcn.2009.27725

Sussman, G., & Anigrass, A. (2000). A study to assess the efficacy of Extend Bar® as an appetite suppressant in males and females. A crossover study in moderately overweight subjects with BMI 27-31 (Final Report). Chicago, IL: University of Chicago.

Suzuki, R., Lee, K., Jing, E., Biddinger, S., McDonald, J., Montine, T., & ... Kahn, C. (2010). Diabetes and insulin in regulation of brain cholesterol metabolism. Cell Metabolism, 12(6), 567-579. doi: 10.1016/j.cmet.2010.11.006

Szwarc, S. (2007, September 15). Are you sure about that? [Web log message]. Junkfood Science [Web log]. Retrieved from

Questions the interpretation of randomized trials, citing critiques of interpretations such as McCormack and Greenhalgh (2000), Ioannidis (2005), and others who show how experts frequently overstate and misinterpret study findings.

Szwarc, S. (2009, May 31). Seeing the evidence: Tighter control of blood sugars in type 2 diabetics [Web log message]. Junkfood Science [Web log]. Retrieved from

Taubes, G. (2002, July 7). What if it's all been a big fat lie? The New York Times Magazine. Retrieved from

Taubes, G. (2003, July 4). Insulin insults may spur Alzheimer's disease. Science, 301(5629), 40. Retrieved July 27, 2008, from Academic Search Premier database.

Taubes, G. (2007, September 24). The scientist and the stairmaster: Why most of us believe that exercise makes us thinner—and why we're wrong. New York Magazine. Retrieved from

Taubes, G. (2007). Good calories, bad calories: Challenging the conventional wisdom on diet, weight control, and disease. New York: Knopf.

Taubes provides a thorough review of 200 years of research on diet and health and demonstrates how various public agencies (e.g,. NIH, AHA) arrived at the some fairly misleading dietary recommendations currently promoted nationwide. He does not push a particular diet or "cure" for overweight. The book reads more like a history and scientific review, and I could not recommend it more highly.

From the book description: "The 11 Critical Conclusions of Good Calories, Bad Calories:

  1. Dietary fat, whether saturated or not, does not cause heart disease.
  2. Carbohydrates do, because of their effect on the hormone insulin. The more easily-digestible and refined the carbohydrates and the more fructose they contain, the greater the effect on our health, weight, and well-being.
  3. Sugars—sucrose (table sugar) and high fructose corn syrup specifically—are particularly harmful. The glucose in these sugars raises insulin levels; the fructose they contain overloads the liver.
  4. Refined carbohydrates, starches, and sugars are also the most likely dietary causes of cancer, Alzheimer's Disease, and the other common chronic diseases of modern times.
  5. Obesity is a disorder of excess fat accumulation, not overeating and not sedentary behavior.
  6. Consuming excess calories does not cause us to grow fatter any more than it causes a child to grow taller.
  7. Exercise does not make us lose excess fat; it makes us hungry.
  8. We get fat because of an imbalance—a disequilibrium—in the hormonal regulation of fat tissue and fat metabolism. More fat is stored in the fat tissue than is mobilized and used for fuel. We become leaner when the hormonal regulation of the fat tissue reverses this imbalance.
  9. Insulin is the primary regulator of fat storage. When insulin levels are elevated, we stockpile calories as fat. When insulin levels fall, we release fat from our fat tissue and burn it for fuel.
  10. By stimulating insulin secretion, carbohydrates make us fat and ultimately cause obesity. By driving fat accumulation, carbohydrates also increase hunger and decrease the amount of energy we expend in metabolism and physical activity.
  11. The fewer carbohydrates we eat, the leaner we will be."

Taubes, G. (2011). Why we get fat and what to do about it. New York: Knopf.

Taubes, G. (2011, April 17). Is sugar toxic? The New York Times Magazine, MM47. Retrieved from

Tinker, L. F., Bonds, D. E., Margolis, K. L., Manson, J. E., Howard, B. V., Larson, J., Perri, M. G., Beresford, S. A. A., Robinson, J. G., Rodriguez, B., Stafford, M. M., Wenger, N. K., Stevens, V. J., & Parker, L. M. (2008). Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: The Women's Health Initiative randomized controlled Dietary Modification Trial. Archives of Internal Medicine, 168(14), 1500-1511.

From the Junkfood Science blog by Sandy Szwarc: "After eight years, there were no significant differences in the incidences of more than 30 clinically-documented cancers, heart attacks or strokes, or all-cause mortality. The dieters initially lost some weight but rebounded and their body weights, despite 8 years of watching what they ate, were no statistically different from the women who'd been eating whatever they wanted. Both groups ended up at nearly the identical weights they started with, differing a mere 0.7kg, about one pound." (See another Junkfood Science entry about this paper.)

Unger, R. H. (2008). Reinventing type 2 diabetes: Pathogenesis, treatment, and prevention. Journal of the American Medical Association, 299, 1185-1187.

UK Prospective Diabetes Study (UKPDS) Group. (1998). Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet, 352(9131), 837-853.

This is the study that started the (to date, unfounded) belief that intensive control of blood sugars in patients with type 2 diabetes will reduce the risk of coronary events and mortality, based on a subjective, unblinded ratings of physical signs that have the potential for vision loss, but the study reported no actual differences in vision loss (Szwarc, 2009, May 31). "The UKPDS Study had reported no statistically significant (p=0.44) reduction of all-cause mortality" (Szwarc), nor any other adverse outcome. Szwarc also cites the letter by Dr. Paul Neeskens (BMJ, UKPDS - Emperors New Clothes): "I have read UKPDS 33 over and over and over and am just astounded at the rampant interpretative bias." See also Montori (2009). Very bad.

US Department of Health and Human Services and the US Department of Agriculture. (2005). The report of the dietary guidelines advisory committee on dietary guidelines for Americans, 2005. Washington, DC: Author. Retrieved from HHS:

The advisory committee set out to "conduct an evidence-based review of diet and health. . . . We believe that the scientific documentation for our major messages is done more systematically and meticulously than that of previous Advisory Committees. Our process did not eliminate the need for scientific judgment in resolving issues characterized by conflicting information. However, the Committee considered such issues with care, and came to sound consensus on all questions" (cover letter).

Taubes (2007), however, has raised a number of concerns, so I set out to examine a couple claims from the Report. Under Question 2 in the Carbohydrate section, for example, the Report states that "current evidence suggests that there is no relationship between total carbohydrate intake (minus fiber) and the incidence of either type 1 or type 2 diabetes." More specifically, "does carbohydrate intake predispose to type 2 diabetes? Evidence from four prospective observational studies indicates that it does not (Lundgren et al., 1989; Marshall et al., 1991; Salmeron et al., 1997a, 1997b)" (Part D, Science Base; Section 5, Carbohydrates). Quite surprisingly, the cited articles did not particularly support their conclusion.

Lundgren et al. (1989) concluded that "no specific dietary recommendations can be based on the results of this study" (abstract), which includes the inference that carbohydrates fail to predispose one to type 2 diabetes. Marshall et al. (1991) examined change in fat intake, not carbohydrates, in an case-control study. The lack of an association between carbohydrates and type 2 diabetes, especially in a correlational studies, does not rule out the possibility of the association. It only shows that these two studies did not find it. Furthermore, the Salmeron et al. (1997a, 1997b) studies appear to have come to an opposite conclusion. In the first study, their "findings support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of NIDDM [non-insulin-dependent diabetes mellitus or type 2 diabetes] in men" (abstract, 1997a). The second paper reports that the "results support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of diabetes in women" (abstract, 1997b). Both studies "suggest that grains should be consumed in a minimally refined form to reduce the incidence of diabetes." Finally, the Report states that "further analysis within the Nurses' Health Study indicates that there may be an association between consumption of sugar-sweetened beverages, other than fruit juices, and an increased risk of type 2 diabetes in women. . . ."

It appears, then, that the Report's own sources refute, to some extent, their conclusion that "there is no relationship between total carbohydrate intake (minus fiber) and the incidence of either type 1 or type 2 diabetes." The inconsistencies within the Report, the research cited by Taubes (2007) that supports that specific relationship, and other questions about this report raised by Taubes, calls into question the recommendations from this publication.

van Raalte, D. H., Ouwens, D. M., & Diamant, M. (2009). Novel insights into glucocorticoid-mediated diabetogenic effects: Towards expansion of therapeutic options? European Journal of Clinical Investigation, 39(2), 81-93.

Abstract: "At pharmacological concentrations, glucocorticoids (GCs) display potent anti-inflammatory effects, and are therefore frequently prescribed by physicians to treat a wide variety of diseases. Despite excellent efficacy, GC therapy is hampered by their notorious metabolic side effect profile. Chronic exposure to increased levels of circulating GCs is associated with central adiposity, dyslipidaemia, skeletal muscle wasting, insulin resistance, glucose intolerance and overt diabetes. Remarkably, many of these side-effects of GC treatment resemble the various components of the metabolic syndrome (MetS), in which indeed subtle disturbances in the hypothalamic-pituitary-adrenal (HPA) axis and/or increased tissue sensitivity to GCs have been reported. Recent developments have led to renewed interest in the mechanisms of GC's diabetogenic effects. First, 'selective dissociating glucocorticoid receptor (GR) ligands', which aim to segregate GC's anti-inflammatory and metabolic actions, are currently being developed. Second, at present, selective 11-hydroxysteroid dehydrogenase type 1 (11-HSD1) inhibitors, which may reduce local GC concentrations by inhibiting cortisone to cortisol conversion, are evaluated in clinical trials as a novel treatment modality for the MetS. In this review, we provide an update of the current knowledge on the mechanisms that underlie GC-induced dysmetabolic effects. In particular, recent progress in research into the role of GCs in the pathogenesis of insulin resistance and beta-cell dysfunction will be discussed" (emphasis added).

Wansink, B., Chandon, P. (2006). Meal size, not body size, explains errors in estimating the calorie content of meals. Annals of Internal Medicine, 145, 326-332.

Editors' notes: "everyone underestimated large meals. Overweight people were more likely to order larger meals and therefore to make larger errors."

Westman, E. C., Yancy, W. S., Edman, J. S., Tomlin, K. F., & Perkinds, C. E. (2002). Effect of 6-month adherence to a very low carbohydrate diet program. American Journal of Medicine, 113(1), 30-36.

Conclusions from the abstract: "A very low carbohydrate diet program led to sustained weight loss during a 6-month period." The authors also found improvement in lipid profiles. See also Yancy et al. (2004).

Zoungas, S., Chalmers, J., Neal, B., Billot, L., Q., L., Hirakawa, Y., & ... Matthews, D. R. (2014). Follow-up of blood-pressure lowering and glucose control in Type 2 diabetes. New England Journal of Medicine, 371(15), 1392-1406. doi: 10.1056/NEJMoa1407963

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