Low-cost exercise interventions improve long-term cardiometabolic health independently of a family history of type 2 diabetes: a randomized parallel group trial.

INTRODUCTION: To investigate the effect of an exercise prescription and a 1-year supervised exercise intervention, and the modifying effect of the family history of type 2 diabetes (FH), on long-term cardiometabolic health. RESEARCH DESIGN AND METHODS: For this prospective randomized trial, we recruited non-diabetic participants with poor fitness (n=1072, 30-70 years). Participants were randomly assigned with stratification for FH either in the exercise prescription group (PG, n=144) or the supervised exercise group (EG, n=146) group and compared with a matched control group from the same population study (CON, n=782). The PG and EG received exercise prescriptions. In addition, the EG attended supervised exercise sessions two times a week for 60 min for 12 months. Cardiometabolic risk factors were measured at baseline, 1 year, 5 years, and 6 years. The CON group received no intervention and was measured at baseline and 6 years. RESULTS: The EG reduced their body weight, waist circumference, diastolic blood pressure, and low-density lipoprotein-cholesterol (LDL-C) but not physical fitness (p=0.074) or insulin or glucose regulation (p>0.1) compared with the PG at 1 year and 5 years (p≤0.011). The observed differences were attenuated at 6 years; however, participants in the both intervention groups significantly improved their blood pressure, high-density lipoprotein-cholesterol, and insulin sensitivity compared with the population controls (p≤0.003). FH modified LDL-C and waist circumference responses to exercise at 1 year and 5 years. CONCLUSIONS: Low-cost physical activity programs have long-term beneficial effects on cardiometabolic health regardless of the FH of diabetes. Given the feasibility and low cost of these programs, they should be advocated to promote cardiometabolic health. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT02131701.

Influence of Familial Renal Glycosuria Due to Mutations in the SLC5A2 Gene on Changes in Glucose Tolerance over Time.

Familial renal glycosuria is an inherited disorder resulting in glucose excretion in the urine despite normal blood glucose concentrations. It is most commonly due to mutations in the SLC5A2 gene coding for the glucose transporter SGLT2 in the proximal tubule. Several drugs have been introduced as means to lower glucose in patients with type 2 diabetes targeting SGLT2 resulting in renal glycosuria, but no studies have addressed the potential effects of decreased renal glucose reabsorption and chronic glycosuria on the prevention of glucose intolerance. Here we present data on a large pedigree with renal glycosuria due to two mutations (c.300-303+2del and p.A343V) in the SLC5A2 gene. The mutations, which in vitro affected glucose transport in a cell line model, and the ensuing glycosuria were not associated with better glycemic control during a follow-up period of more than 10 years. One individual, who was compound heterozygous for mutations in the SLC5A2 gene suffered from severe urogenital candida infections and postprandial hypoglycemia. In conclusion, in this family with familial glycosuria we did not find any evidence that chronic loss of glucose in the urine would protect from deterioration of the glucose tolerance over time.

Predictors of and longitudinal changes in insulin sensitivity and secretion preceding onset of type 2 diabetes.

Identification of individuals at high risk of developing type 2 diabetes is a prerequisite for prevention of the disease. We therefore studied risk factors predicting type 2 diabetes in the Botnia Study in Western Finland. A total of 2,115 nondiabetic individuals were prospectively followed with repeated oral glucose tolerance tests. After a median follow-up of 6 years, 127 (6%) subjects developed diabetes. A family history of diabetes (hazard ratio [HR] 2.2, P = 0.008), BMI (HR for comparison of values below or above the median 2.1, P < 0.001), waist-to-height index (2.3, P < 0.001), insulin resistance (2.1, P = 0.0004), and beta-cell function adjusted for insulin resistance (2.7, P < 0.0001) predicted diabetes. Marked deterioration in beta-cell function with modest changes in insulin sensitivity was observed during the transition to diabetes. The combination of FPG > or =5.6 mmol/l, BMI > or =30 kg/m(2), and family history of diabetes was a strong predictor of diabetes (3.7, P < 0.0001). Of note, using FPG > or =6.1 mmol/l or 2-h glucose > or =7.8 mmol/l did not significantly improve prediction of type 2 diabetes. In conclusion, a marked deterioration in beta-cell function precedes the onset of type 2 diabetes. These individuals can be identified early by knowledge of FPG, BMI, and family history of diabetes.