Are the determinants of the progression to type 2 diabetes and regression to normoglycemia in the populations with pre-diabetes the same?

Abstract

BackgroundWe aimed to determine the predictors of regression to normoglycemia and progression to diabetes among subjects with pre-diabetes in a single model concurrently.MethodsThe present study included 1329 participants aged 20 to 70 years with prediabetes from the population-based cohort of the Tehran Lipid and Glucose Study, with a 10-year follow-up. Glycemic status at follow-up was categorized as regression to normoglycemia: fasting plasma glucose [FPG] of <5.55 and 2h-plasma glucose [PG] of <7.77 mmol/L, and not taking antidiabetic medications. Glycemic status at follow-up was categorized as progression to diabetes: FPG ≥7 or 2h-PG of ≥11.1 mmol/L, or taking antidiabetic medications. Glycemic status determined whether the patients remained in prediabetes category (isolated impaired fasting glycaemia [iIFG] [(5.55≤FPG<7 and 2h-PG<7.77 mmol/L); isolated impared glucose tolarence [iIGT] (7.77 ≤ 2h-PG<11.1 and FGP<5.55 mmol/L)]. With prediabetes as a reference, multinomial logistic regression was utilized to identify the determinants of glycemic changes.ResultsApproximately 40% of participants returned to normoglycemia (n = 578), and similar percentage of participants progressed to diabetes (n = 518). Based on the multivariable multinomial model, regression to normoglycemia was associated with age (relative risk ratio [RRR] = 0.97; 95% CI, 0.95-0.99), female sex (RRR = 1.72; 95% CI, 1.18-2.50), high education level of ≥12 years (RRR = 2.10; 95% CI, 1.19-3.70), and combined IFG/impaired glucose tolerance (IGT) versus IFG (RRR = 0.45; 95% CI, 0.29-0.70). The risk of progression to diabetes increased with body mass index (RRR = 1.10; 95% CI, 1.05-1.15), waist circumference (RRR = 0.97; 95% CI, 0.96-0.99), positive familial history of diabetes (RRR = 1.62; 95% CI, 1.07-2.45), and combined IFG/IGT versus IFG (RRR = 2.54; 95% CI, 1.71-3.77).ConclusionA small percentage of patients with prediabetes remain in this condition, but the majority go on to develop diabetes or regress to normoglycemia. Both directions had distinct predictors.

Diabetes, COVID‐19, and questions unsolved

“…61 The underlying pathophysiology is yet to be firmly established, but there is some suggestion that the physiologic stress response may play a role, especially given that a considerable proportion (40%) of people regress to normoglycaemia within a year. 62 However, when compared with other conditions that provoke a stress response, patients with severe COVID-19 demonstrate significantly and disproportionately higher insulin requirements, alluding to a potential diabetogenic effect. 63,64 Current theories for this include COVID-19-induced autoimmune and inflammatory insult to pancreatic beta cells, and insulin resistance as the consequence of mACE2-virus binding.…”

“…Concerningly, people with new onset diabetes appear to be at an increased risk of mortality and adverse events compared with people with known diabetes and without diabetes 61 . The underlying pathophysiology is yet to be firmly established, but there is some suggestion that the physiologic stress response may play a role, especially given that a considerable proportion (40%) of people regress to normoglycaemia within a year 62 . However, when compared with other conditions that provoke a stress response, patients with severe COVID‐19 demonstrate significantly and disproportionately higher insulin requirements, alluding to a potential diabetogenic effect 63,64 .…”

Differential effect of interventions in patients with prediabetes stratified by a machine learning‐based diabetes progression prediction model

“…Several interventions were shown to be effective in diabetes prevention in participants with prediabetes, such as intensive lifestyle therapy and medications, including metformin, 5 pioglitazone 6 and acarbose 7 . In fact, only ~5%–10% of participants without intervention progressed to diabetes every year, 8,9 yet the progression to type 2 diabetes in participants with prediabetes was highly heterogeneous 10 . Currently, clinical guidelines only suggest metformin treatment for prediabetes in a few patients [e.g.…”

“…7 In fact, only $5%-10% of participants without intervention progressed to diabetes every year, 8,9 yet the progression to type 2 diabetes in participants with prediabetes was highly heterogeneous. 10 Currently, clinical guidelines only suggest metformin treatment for prediabetes in a few patients [e.g. those with body mass index (BMI) ≥35 kg/m 2 , those aged <60 years or women with gestational diabetes].…”

Failure to decrease HbA1c levels following TB treatment is associated with elevated Th1/Th17 CD4+ responses

“…Although not all individuals with prediabetes go on to develop overt diabetes ( 12 – 15 ), the alterations in immune function in persons with prediabetes and DM that contribute to active TB disease overlap, in part, with studies linking immunologic biomarkers to the development of metabolic disease in the absence of infectious conditions. In the general population, a reduced proportion of naïve and regulatory (T reg ) CD4+ T cells ( 16 – 18 ), higher circulating memory CD4+ T cells ( 16 , 19 ), and a shift towards pro-inflammatory Th1 and Th17 helper cells ( 18 ) was associated with prevalent diabetes.…”