Less but better: cardioprotective lipid profile of patients with GCK-MODY despite lower HDL cholesterol level

Patients with diabetes caused by single-gene mutations generally exhibit an altered course of diabetes. Those with mutations of the glucokinase gene (GCK-MODY) show good metabolic control and low risk of cardiovascular complications despite paradoxically lowered high-density lipoprotein (HDL) cholesterol levels. In order to investigate the matter, we analyzed the composition of low-density lipoprotein (LDL) and HDL subpopulations in such individuals. The LipoPrint(©) system (Quantimetrix, USA) based on non-denaturing, linear polyacrylamide gel electrophoresis was used to separate and measure LDL and HDL subclasses in fresh-frozen serum samples from patients with mutations of glucokinase or HNF1A, type 1 diabetes (T1DM) and healthy controls. Fresh serum samples from a total of 37 monogenic diabetes patients (21 from GCK-MODY and 16 from HNF1A-MODY), 22 T1DM patients and 15 healthy individuals were measured in this study. Concentrations of the small, highly atherogenic LDL subpopulation were similar among the compared groups. Large HDL percentage was significantly higher in GCK-MODY than in control (p = 0.0003), T1DM (p = 0.0006) and HNF1A-MODY groups (p = 0.0246). Patients with GCK-MODY were characterized by significantly lower intermediate HDL levels than controls (p = 0.0003) and T1DM (p = 0.0005). Small, potentially atherogenic HDL content differed significantly with the GCK-MODY group showing concentrations of that subfraction from control (p = 0.0096), T1DM (p = 0.0193) and HNF1A-MODY (p = 0.0057) groups. Within-group heterogeneity suggested the existence of potential gene–gene or gene–environment interactions. GCK-MODY is characterized by a strongly protective profile of HDL cholesterol subpopulations. A degree of heterogeneity within the groups suggests the existence of interactions with other genetic or clinical factors

Metabolic profile in two physically active Inuit groups consuming either a western or a traditional Inuit diet

OBJECTIVES: To evaluate the effect of regular physical activity on metabolic risk factors and blood pressure in Inuit with high BMI consuming a western diet (high amount of saturated fatty acids and carbohydrates with a high glycemic index). STUDY DESIGN: Cross sectional study, comparing Inuit eating a western diet with Inuit eating a traditional diet. METHODS: Two physically active Greenland Inuit groups consuming different diet, 20 eating a traditional diet (Qaanaaq) and 15 eating a western diet (TAB), age (mean (range)); 38, (22–58) yrs, BMI; 28 (20–40) were subjected to an oral glucose tolerance test (OGTT), blood sampling, maximal oxygen uptake test, food interview/collection and monitoring of physical activity. RESULTS: All Inuit had a normal OGTT. Fasting glucose (mmol/l), HbA1c (%), total cholesterol (mmol/l) and HDL-C (mmol/l) were for Qaanaaq women: 4.8±0.2, 5.3±0.1, 4.96±0.42, 1.34±0.06, for Qaanaaq men: 4.9±0.1, 5.7±0.1, 5.08±0.31, 1.28±0.09, for TAB women: 5.1±0.2, 5.3±0.1, 6.22±0.39, 1.86±0.13, for TAB men: 5.1±0.2, 5.3±0.1, 6.23±0.15, 1.60±0.10. No differences were found in systolic or diastolic blood pressure between the groups. There was a more adverse distribution of small dense LDL-C particles and higher total cholesterol and HDL-C concentration in the western diet group. CONCLUSIONS: Diabetes or impaired glucose tolerance was not found in the Inuit consuming either the western or the traditional diet, and this could, at least partly, be due to the high amount of regular daily physical activity. However, when considering the total cardio vascular risk profile the Inuit consuming a western diet had a less healthy profile than the Inuit consuming a traditional diet

Myocardial Tissue Remodeling in Adolescent Obesity

Background-Childhood obesity is a significant risk factor for cardiovascular disease in adulthood. Although ventricular remodeling has been reported in obese youth, early tissue-level markers within the myocardium that precede organ-level alterations have not been described. Methods and Results-We studied 21 obese adolescents (mean age, 17.7 +/- 2.6 years; mean body mass index [BMI], 41.9 +/- 9.5 kg/m(2), including 11 patients with type 2 diabetes [T2D]) and 12 healthy volunteers (age, 15.1 +/- 4.5 years; BMI, 20.1 +/- 3.5 kg/m(2)) using biomarkers of cardiometabolic risk and cardiac magnetic resonance imaging (CMR) to phenotype cardiac structure, function, and interstitial matrix remodeling by standard techniques. Although left ventricular ejection fraction and left atrial volumes were similar in healthy volunteers and obese patients (and within normal body size-adjusted limits), interstitial matrix expansion by CMR extracellular volume fraction (ECV) was significantly different between healthy volunteers (median, 0.264; interquartile range [IQR], 0.253 to 0.271), obese adolescents without T2D (median, 0.328; IQR, 0.278 to 0.345), and obese adolescents with T2D (median, 0.376; IQR, 0.336 to 0.407; P=0.0001). ECV was associated with BMI for the entire population (r=0.58, P<0.001) and with high-sensitivity C-reactive protein (r=0.47, P<0.05), serum triglycerides (r=0.51, P<0.05), and hemoglobin A1c (r=0.76, P<0.0001) in the obese stratum. Conclusions-Obese adolescents (particularly those with T2D) have subclinical alterations in myocardial tissue architecture associated with inflammation and insulin resistance. These alterations precede significant left ventricular hypertrophy or decreased cardiac function.24Harvard CatalystHarvard Clinical and Translational Science Center (National Center for Research Resources)Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]Harvard UniversityAmerican Heart Association [11POST000002, 12FTF12060588]Heart Failure NIH Clinical Research Network [U01-HL084877]NIH [R01-HL091157]Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]American Heart Association [11POST000002, 12FTF12060588]Heart Failure NIH Clinical Research Network [U01-HL084877]NIH [R01-HL091157

Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women

<p>Abstract</p> <p>Background</p> <p>Intermittent fasting (IF; severe restriction 1 d/week) facilitates weight loss and improves coronary heart disease (CHD) risk indicators. The degree to which weight loss can be enhanced if IF is combined with calorie restriction (CR) and liquid meals, remains unknown.</p> <p>Objective</p> <p>This study examined the effects of IF plus CR (with or without a liquid diet) on body weight, body composition, and CHD risk.</p> <p>Methods</p> <p>Obese women (n = 54) were randomized to either the IFCR-liquid (IFCR-L) or IFCR-food based (IFCR-F) diet. The trial had two phases: 1) 2-week weight maintenance period, and 2) 8-week weight loss period.</p> <p>Results</p> <p>Body weight decreased more (P = 0.04) in the IFCR-L group (3.9 ± 1.4 kg) versus the IFCR-F group (2.5 ± 0.6 kg). Fat mass decreased similarly (P < 0.0001) in the IFCR-L and IFCR-F groups (2.8 ± 1.2 kg and 1.9 ± 0.7 kg, respectively). Visceral fat was reduced (P < 0.001) by IFCR-L (0.7 ± 0.5 kg) and IFCR-F (0.3 ± 0.5 kg) diets. Reductions in total and LDL cholesterol levels were greater (<it>P</it> = 0.04) in the IFCR-L (19 ± 10%; 20 ± 9%, respectively) versus the IFCR-F group (8 ± 3%; 7 ± 4%, respectively). LDL peak particle size increased (P < 0.01), while heart rate, glucose, insulin, and homocysteine decreased (P < 0.05), in the IFCR-L group only.</p> <p>Conclusion</p> <p>These findings suggest that IF combined with CR and liquid meals is an effective strategy to help obese women lose weight and lower CHD risk.</p