Type 2 diabetes

type-2

Type 2 diabetes - the evidence

This guide is written by Dr. Andreas Eenfeldt, MD and was last updated on June 17, 2022. It was medically reviewed by Dr. Bret Scher, MD on April 3, 2020.

The guide contains scientific references. You can find these in the notes throughout the text, and click the links to read the peer-reviewed scientific papers. When appropriate we include a grading of the strength of the evidence, with a link to our policy on this. Our evidence-based guides are updated at least once per year to reflect and reference the latest science on the topic.

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  1. Type 1, usually diagnosed in kids, makes up the rest. However, there are two other forms of diabetes. Latent Autoimmune Diabetes of Adults LADA is a form that has been described as “halfway between type 1 and type 2.” As with type 1 you have antibodies that attack the insulin producing beta cells. LADA usually debuts later in life then type 1 and develops more slowly. Maturity onset diabetes of the young, MODY, is a rarer form that is caused by a genetic abnormality and also mimics type 1 but is diagnosed in adults.

    BMJ 2018: Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: population based study [observational study, weak evidence]

  2. Diabetes 2018: Global prevalence of type 2 diabetes over the next ten years (2018-2028) [review of observational studies; weak evidence]

    Medicine 2014: Epidemiology of diabetes [review of observational studies; weak evidence]

  3. BMJ 2018: Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: population based study [observational study; weak evidence]

  4. World Journal of Diabetes 2013 Type 2 diabetes mellitus in children and adolescents. [overview article; ungraded]

  5. Diabetes Care 1992: Pathogenesis of NIDDM. A balanced overview. [overview article; ungraded]

  6. American Journal of Clinical Nutrition 1992: Surgical treatment of obesity and its effect on diabetes: 10-y follow-up. [observational study, weak evidence]

    Diabetes Care 2012: Diabetes: Have we got it all wrong? [overview article; ungraded]

  7. Although this is still controversial for some, the following review article summarizes insulin’s role in obesity, and the subsequent reference shows how inhibiting insulin secretion aids in weight loss. Taken together, it seems very likely that insulin has a direct action of increasing obesity.
    Journal of Endocrinology 2017: A causal role for hyperinsulinemia in obesity. [overview article; ungraded]

    International Journal of Obesity Related Metabolic Disorders 2003: Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults [observational study, weak evidence]

  8. PLoS One 2013: The relationship of sugar to population-level diabetes prevalence: an econometric analysis of repeated cross-sectional data. [observational study, weak evidence]

    BMC Public Health 2014: Per capita sugar consumption and prevalence of diabetes mellitus–global and regional associations. [observational study, weak evidence]

  9. PLoS Biology 2018: Glucotypes reveal new patterns of glucose dysregulation. [nonrandomized study, weak evidence]

  10. American Journal of Clinical Nutrition 2008: Glycemic index, glycemic load, and chronic disease risk–a meta-analysis of observational studies. [observational study, weak evidence]

  11. Nutrients 2018: The effect of dietary glycaemic index on glycaemia in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. [strong evidence]

    PLoS One 2014: A randomized pilot trial of a moderate carbohydrate diet compared to a very low carbohydrate diet in overweight or obese individuals with type 2 diabetes mellitus or prediabetes. [randomized trial; moderate evidence]

  12. European Journal of Clinical Nutrition 1992: Classification and measurement of nutritionally important starch fractions. [mechanistic study article; ungraded]

    The following RCT showed that all types of bread, including sprouted and multi-grain, caused an elevation in blood sugar and serum insulin levels.

    Journal of Nutrition and Metabolism 2012: The acute impact of ingestion of sourdough and whole-grain breads on blood glucose, insulin, and incretins in overweight and obese men. [randomized trial; moderate evidence]

  13. Diabetes Care 2019: Nutrition therapy for adults with diabetes or prediabetes: a consensus report [overview article; ungraded]

  14. Annals of Internal Medicine 2005: Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes. [observational study, weak evidence]

  15. Nutrition and Diabetes 2017: Enhanced insulin sensitivity in successful, long-term weight loss maintainers compared with matched controls with no weight loss history. [nonrandomized study, weak evidence]

  16. Some disagree with the use of the word “reverse” when it comes to type 2 diabetes. The concern is that it may imply the disease is completely gone, never to return. At Diet Doctor, we use the term “reverse” to indicate that the diagnosis of diabetes is no longer present at that moment. However, we acknowledge that the diagnosis of diabetes will likely return if a patient goes back to their prior high-carb eating habits. Therefore, “reverse” does not imply a cure. Instead, it identifies a successful intervention that, if maintained, will likely keep the disease at bay.

    The following study showed a ketogenic diet was effective at reversing diabetes or reducing medications in the majority of subjects.

    Frontiers in Endocrinology 2019: Long-term effects of a novel continuous remote care intervention including nutritional ketosis for the management of type 2 diabetes: A 2-year non-randomized clinical trial [weak evidence]

  17. This is based on consistent clinical experience of low-carb practitioners. [weak evidence]

  18. Nutrition Research 2011: Prevalence and correlates of vitamin D deficiency in US adults. [observational study, weak evidence]

  19. Although there is conflicting data on the subject, these studies suggest a potential benefit from vitamin D supplementation

    Nutrition Journal 2012: A 12-week double-blind randomized clinical trial of vitamin D3 supplementation on body fat mass in healthy overweight and obese women [moderate evidence]

    Journal of the American College of Nutrition 2016: The effect of vitamin D supplementation on glycemic control and lipid profile in patients with type 2 diabetes mellitus. [noncontrolled study, weak evidence]

  20. NEJM 2008: Effects of intensive glucose lowering in type 2 diabetes. [randomized trial; moderate evidence]

    The Lancet 2010: Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study [observational study; weak evidence]

    However, more recent trials of the drug class SGLT2 inhibitors do show an improvement in cardiovascular outcomes and risk of death. One hypothesis is that these drugs lower insulin levels whereas older drugs increased insulin levels.

    NEJM 2015: Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. [randomized trial; moderate evidence]

    Cardiovascular Ultrasound 2019: Effect of sodium glucose cotransporter 2 inhibitors on cardiac function and cardiovascular outcome: a systematic review [overview article; ungraded]

  21. The studies that show no improvement with more intensive medications included insulin and medications that increased insulin. Newer drugs, like the SGLT2 inhibitors, can lower insulin and have been shown to improve risk of heart disease or overall mortality. Since lifestyle interventions, like low-carb diets and exercise, also lower both glucose and insulin, one could assume they would likewise show beneficial results although this has yet to be studied in adequately designed long-term trials.

    The following trial, called the LOOK AHEAD trial, is frequently cited as evidence that lifestyle interventions do not improve clinical outcomes in patients with diabetes. However, the intervention was general calorie reduction and did not address carbohydrate intake.

    NEJM 2013: Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. [randomized trial; moderate evidence]

  22. JNCI Cancer Spectrum 2017: The effect of metformin on mortality among cancer patients with diabetes: A systematic review and meta-analysis [review of observational studies, weak evidence]

  23. Experimental and Therapeutic Medicine 2016: Association between insulin dosage and insulin usage time, and coronary artery lesions in patients with type 2 diabetes and coronary heart disease [observational study, weak evidence]

    European Heart Journal 2007: The impact of glucose lowering treatment on long-term prognosis in patients with type 2 diabetes and myocardial infarction: a report from the DIGAMI 2 trial [observational study, weak evidence]

    Diabetologia 2009: The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. [observational study, weak evidence]

    NEJM 2008: Effects of intensive glucose lowering in type 2 diabetes. [randomized trial; moderate evidence]

  24. NEJM 2015: Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. [randomized trial; moderate evidence]

  25. Diabetes Care 2015: Euglycemic diabetic ketoacidosis: A predictable, detectable, and preventable safety concern with SGLT2 inhibitors[case reports; very weak evidence]

  26. Journal of Endocrinology and Metabolism 1997: Effect of obesity on the response to insulin therapy in noninsulin-dependent diabetes mellitus. [nonrandomized study, weak evidence]

    Nature Medicine 2017: Insulin action and resistance in obesity and type 2 diabetes. [overview article; ungraded]

  27. Nutrition & Diabetes 2017: Twelve-month outcomes of a randomized trial of a moderate-carbohydrate versus very low-carbohydrate diet in overweight adults with type 2 diabetes mellitus or prediabetes [moderate evidence]

    Diabetes Therapy 2018: Effectiveness and safety of a novel care model for the management of type 2 diabetes at 1 year: an open-label, non-randomized, controlled study [weak evidence]

  28. With insulin-treated diabetes it’s important to monitor your blood sugar closely in the beginning when starting an LCHF diet! A diet including few carbohydrates usually causes a greatly reduced need for insulin. It’s then important to adjust (lower) the doses sufficiently to avoid blood sugar droping too low. This should always be done with support of your physician or diabetes nurse.

  29. Some disagree with the use of the word “reverse” when it comes to type 2 diabetes. The concern is that it may imply the disease is completely gone, never to return. At Diet Doctor, we use the term “reverse” to indicate that the diagnosis of diabetes is no longer present at that moment. However, we acknowledge that the diagnosis of diabetes will likely return if a patient goes back to their prior high-carb eating habits. Therefore, “reverse” does not imply a cure. Instead, it identifies a successful intervention that, if maintained, will likely keep the disease at bay.

  30. Diabetes Therapy 2018: Effectiveness and safety of a novel care model for the management of type 2 diabetes at 1 year: an open-label, non-randomized, controlled study [weak evidence]

    The longest published study yet on low carb for type 2 diabetes, is a non-randomized intervention trial of a 20% carbohydrate diet for people with obesity and type 2 diabetes. They published a 44-month follow-up showing continued good results on A1c, weight, and reduction of diabetes medications:

    Nutrition & Metabolism 2008: Low-carbohydrate diet in type 2 diabetes: stable improvement of bodyweight and glycemic control during 44 months follow-up [weak evidence]

  31. [anecdotal report; very weak evidence]

  32. [anecdotal report; very weak evidence]

  33. BMJ 2012: Meta-analysis of individual patient data in randomised trials of self monitoring of blood glucose in people with non-insulin treated type 2 diabetes. [systematic review of randomized trials; strong evidence]

  34. Clinical Diabetes 2011: Microvascular and macrovascular complications of diabetes [overview article; ungraded]