Skinny patients with type 2 diabetes?

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Author: Jerrine Fletcher, PhD Candidate in Pharmacy, Florida A&M University College of Pharmacy and Pharmaceutical Sciences

Patients with lean body types / normal BMI and indication of type 2 diabetes.

Type 2 diabetes is classified into groups of insulin resistant or insulin deficient phenotypes. There is a strong correlation between type 2 diabetes and the main hallmark of obesity or being overweight. However, a significant fraction of lean individuals, with an average body mass index of 29 kg / m2, develops type 2 diabetes.

The Journal of Clinical Endocrinology and Metabolism published a study of women with gestational diabetes who developed prediabetes or overt diabetes ten months after giving birth, and women who had normal glucose tolerance after gestational diabetes. The study reported that almost half of patients with prediabetes or type 2 diabetes had a low and permanently normal BMI of around 22 kg / m2, low waist circumference, normal triglyceride levels and liver fat content less than 1%. In addition, the condition of these patients could not be explained by insulin deficiency or beta cell dysfunction, as they exhibited a mixed phenotype of deficient insulin secretion and insulin resistance.

In patients with prediabetes, insulin secretion characterized by an acute insulin response is usually lost in many cases. However, lean women with prediabetes have a normal critical insulin response. This response suggests preserved beta cell function. The oral glucose tolerance test also confirmed this finding as there were intact C peptide responses within the first 30 minutes, indicating a rapid response to insulin. However, there was some beta cell dysfunction due to documented increases in fasting blood sugar or impaired glucose tolerance.

The study also looked at the origins of insulin resistance and showed components of hepatic and muscle insulin resistance compared to controls. The oral glucose tolerance test was used to calculate hepatic insulin resistance using the algorithm of Abdul-Ghani and colleagues. The increase in liver fat is usually related to hepatic insulin resistance. However, many post-gestational diabetic patients with prediabetes or T2DM with less than 1% liver fat content have shown hepatic insulin resistance. Hepatic insulin resistance is quickly lost in obese patients with fatty liver disease if their calorie intake is restricted. In lean patients, however, this type of energy overload would not be expected. To establish actual hepatic insulin resistance in lean subjects, insulin sensitivity, including measurements of hepatic glucose production and lipogenesis, will need to be addressed more directly. In a study of type 2 diabetes, hepatic lipogenesis was linked to remission and relapse of diabetes. An interesting aspect could be to use the palmitate fraction in very low density lipoprotein derived from the liver as a marker for hepatic lipogenesis.

Free fatty acids were significantly increased in lean post-gestational diabetic women with glycemic disturbances. These patients had normal triglycerides and a high density lipoprotein-cholesterol and hepatic fat content of less than 1%. Thus, the presence of free fatty acids in lean patients may indicate lipolysis of the peripheral fatty tissue. Peripheral fat tissue lipolysis may be related to some degree of insulin resistance of fat tissue, which may affect whole body and liver insulin sensitivity.

In the Whitehall II study, a large subset of participants with type 2 diabetes had a similar lean phenotype without metabolic syndrome. This study made it possible to establish a more complete representation of this phenotype. Studies conducted with lean patients do not agree with each other. Some studies report that normal-weight patients have a low risk of progression to type 2 diabetes and cardiovascular disease. Others report a higher risk of rapid decline in beta cell function and cardiovascular disease.

Diabetic patients who have impaired fasting blood sugar and glucose intolerance are more likely to avoid the onset of T2DM than patients with glucose intolerance. In the diabetes prevention program, metformin was found to be more effective in preventing the onset of diabetes in women with gestational diabetes than in any other group. This effect, however, was significant in obese participants.

A weaker VO2 max has been linked to less physical activity. In this report, lean prediabetic women had lower VO2 maximum, and these patients are recommended to increase their physical activity and reduce their free fatty acids. Exercise appears to be more effective in patients with impaired fasting blood sugar only or impaired glucose tolerance, and not a combination of the two. Further studies should be carried out with lean patients and young patients without metabolic syndrome. There is no definitive answer on the impact of specific treatments on the different subtypes of prediabetes in patients.

Practice the beads:

  • Type 2 diabetes is strongly associated with obesity; however, many lean patients develop type 2 diabetes.
  • Metformin was most effective in preventing the development of type 2 diabetes in women with gestational diabetes.
  • An acute insulin response was expected in lean women with prediabetes. However, the critical insulin response is usually lost in many cases of prediabetes.

Pfeiffer, Andreas FH and Stefan Kabisch. “Lean (pre) diabetes – Underestimated and underexplored. “The Journal of Clinical Endocrinology and Metabolism vol. 106.8 (2021): e3278-e3280. Doi: 10.1210 / clinem / dgab198

Jerrine Fletcher, fourth year PhD candidate, Florida A&M University College of Pharmacy

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