A Pathophysiology of Type 2 Diabetes Unrelated to Metabolic Syndrome

Abstract

Objective Clinically, type 2 diabetes mellitus (T2DM) is heterogeneous, but the prevailing pathophysiologic hypothesis nevertheless contends that components of metabolic syndrome are central to all cases of T2DM. Here, we reevaluated this hypothesis. Research Design and Methods We conducted a cross-sectional analysis of 138 women from the monocenter, post gestational diabetes study PPSDiab, 73 of which had incident prediabetes or T2DM. Additionally, we examined all the 412 incident cases of T2DM in phases 3-9 of the Whitehall II Study in comparison to healthy controls. Our analysis included a medical history, anthropometrics, oral glucose tolerance testing, and laboratory chemistry in both studies. Additional analyses from the PPSDiab Study consisted of cardiopulmonary exercise testing, magnetic resonance imaging, auto-antibody testing, and the exclusion of glucokinase maturity-onset diabetes of the young. Results We found that 33 (45%) of the women with prediabetes or T2DM in the PPSDiab Study displayed no components of metabolic syndrome. They reached no point for metabolic syndrome in the NCEP ATP3 score other than hyperglycemia and, moreover, had levels of liver fat content, plasma triglycerides, hdl cholesterol, c-reactive protein, and blood pressure that were comparable to healthy controls. In the Whitehall II Study, 62 (15%) of the incident T2DM cases fulfilled the same criteria. In both studies, these cases without metabolic syndrome revealed insulin resistance and inadequately low insulin secretion. Conclusions Our results contradict the hypothesis that components of metabolic syndrome are central to all cases of T2DM. Instead, they suggest the common occurrence of a second, unrelated pathophysiology.

Altered Circulating Leptin, hGH, and IGF-I in Prediabetes and Screening-Diagnosed T2DM Unrelated to Metabolic Syndrome in Women Post Gestational Diabetes

“…First, we compared the 3 groups of women in this study (Table 1). The clinical parameters in the top part of the table have been reported previously [1].…”

“…The study cohort for this analysis is the same PPSDiab cohort as in the previous publication of Rottenkolber and colleagues [1] and has been described there in detail. In brief, the cohort consists of women consecutively recruited 3-16 months after a pregnancy, either with GDM or with normoglycemia.…”

Health impact of seven herpesviruses on (pre)diabetes incidence and HbA1c: results from the KORA cohort

“…Both viruses cause chronic infections and potentially modulate the immune system [ 30 ], which in turn influences the endocrine system. It has been established that there are other as yet unknown causes of type 2 diabetes development besides the metabolic syndrome [ 31 ].…”

Lean (Pre)Diabetes – Underestimated and Underexplored

“…A study in this issue of the Journal of Clinical Endocrinology & Metabolism ( 2 ) carefully characterized women with gestational diabetes who developed prediabetes or manifest diabetes 10 months after delivery and women who had normal glucose tolerance after gestational diabetes. Remarkably, almost half of the participants with prediabetes or T2DM had a low and definitively normal BMI of around 22 kg/m 2 , normal triglyceride levels, low waist circumference, and a liver fat content below 1% as determined by determined by magnetic resonance imaging and spectroscopy.…”

“…In lean post-GDM women with glycemic disturbance, a potentially contributing metabolic factor despite normal triglycerides and high-density lipoprotein–cholesterol and liver fat content below 1% were markedly increased free fatty acids ( 2 ). Since free fatty acids in lean subjects reflect peripheral adipose tissue lipolysis, this may indicate some degree of adipose tissue insulin resistance which is known to impair whole body and hepatic insulin sensitivity.…”