Physical Fitness and Cardiovascular Risk Factors in Novel Diabetes Subgroups

Abstract

Context Physical inactivity promotes insulin resistance and increases the risk of diabetes and cardiovascular disease. Recently introduced clustering based on simple clinical measures identified diabetes subgroups (clusters) with different risks of diabetes-related comorbidities and complications. Objective This study aims to determine differences in physical fitness and cardiovascular risk between diabetes subgroups and a glucose-tolerant control group (CON). We hypothesized that the severe insulin-resistant diabetes (SIRD) subgroup associates with lower physical fitness and increased cardiovascular risk. Methods Physical fitness and cardiovascular risk of 746 participants with recent-onset diabetes (diabetes duration of <12 months, aged 18-69 years) and 74 CON of the German Diabetes Study (GDS), a prospective longitudinal cohort study, were analyzed. Main outcome measures included physical fitness (VO2max from spiroerogometry), endothelial function (flow- and nitroglycerin-mediated dilation) and cardiovascular risk scores (Framingham Risk Scores for Coronary Heart Disease (FRS-CHD) and Atherosclerotic CardioVascular Disease (ASCVD) risk score). Results VO2max was lower in SIRD than in CON, severe autoimmune diabetes (SAID) (both p<0.001) and mild age-related diabetes (MARD) (p<0.01) subgroups, but not different compared to severe insulin-deficient diabetes (SIDD) (p=0.98) and moderate obesity-related diabetes (MOD) subgroups (p=0.07) after adjustment for age, sex and BMI. Endothelial function was similar among all groups, whereas SAID had lower FRS-CHD and ASCVD than SIRD, MOD and MARD (all p<0.001). Conclusions Despite comparable endothelial function across all groups, SIRD showed the lowest physical fitness. Of note, SAID had the lowest cardiovascular risk within the first year after diabetes diagnosis compared to the other diabetes subgroups.

Metabolic Factors Predict Changes in Endothelial Function During the Early Course of Type 1 and Type 2 Diabetes

“…While recent meta-analyses showed impaired endothelial function in T1D ( 26 ) and T2D compared with healthy people ( 27 ), another recent population-based study suggested no association between diabetes and endothelial function ( 11 ). Previous studies reported reduced FMD only for overt T2D, but not for participants with impaired glucose tolerance ( 28 ) or at the time of diabetes onset ( 19 ). The present study adds to these data that endothelial dysfunction may not be necessarily present at diagnosis, but rapidly develop despite only minor changes in fat mass and glycemic control, and no changes in lipid profile in metabolically well-controlled patients with T2D during 5 years.…”

“…Images of the brachial artery were obtained before and 3 minutes after administration. FMD and NMD were calculated as the quotient between the arterial baseline diameter and the diameter after cuff deflation and after medication administration, respectively, using Brachial-Analyzer software (Medical Imaging Applications, Coralville, Iowa, USA) ( 19 ). All data underwent intensive quality control check.…”

Twenty‐four‐hour physical behaviour profiles across type 2 diabetes mellitus subtypes

“…The independent effects of physical activity are relevant to our findings and extend to others that have investigated differences across T2DM subtypes. For instance, previous research conducted in 746 participants with recent‐onset T2DM (<12 months), demonstrated that those in the OB cluster display a low cardiorespiratory fitness level, relative to both control (non‐T2DM) and other T2DM clusters 39 . As such individuals are prime candidates for targeted lifestyle interventions, it is important not to focus on the potential for weight loss as the sole outcome from increasing physical activity/fitness levels, but rather to suggest that it influences the composition and maintenance of weight loss alongside other key health metrics (e.g., HbA1c).…”

“…38 The independent effects of physical activity are relevant to clusters. 39 As such individuals are prime candidates for targeted lifestyle interventions, it is important not to focus on the potential for weight loss as the sole outcome from increasing physical activity/ fitness levels, but rather to suggest that it influences the composition and maintenance of weight loss alongside other key health metrics (e.g., HbA1c).…”

Deletion of Tbc1d4/As160 abrogates cardiac glucose uptake and increases myocardial damage after ischemia/reperfusion

“…T2DM is associated with an elevated risk for CVD and poor recovery after MI. Notably, severe insulin resistance found in a subset of patients with diabetes is highly associated with cardiovascular complications [27], however, the molecular mechanisms linking insulin action and heart disease are not well understood. In the present study, we demonstrate that lack of the insulin signaling protein TBC1D4 in mice abrogates cardiac glucose uptake in response to insulin and aggravates cardiac damage after myocardial infarction.…”