Long-term glycaemic control with insulin glargine in Type 2 diabetes.

OBJECTIVE: This study examined the long-term glycaemic control and safety of insulin glargine (LANTUS) in patients with Type 2 diabetes. STUDY DESIGN AND METHODS: This

Validity and reproducibility of an interviewer-administered food frequency questionnaire in Austrian adults at risk of or with overt diabetes mellitus.

Food frequency questionnaires (FFQs) provide an inexpensive tool for dietary assessment. Given the scarcity of data on their validity for nutritional analysis in persons with overt diabetes mellitus or with increased risk of diabetes (relatives of patients with diabetes), this study tests the hypothesis that an FFQ, adapted to local dietary habits, yields a reliable estimate of nutrient intake when compared with 7-day food record (7DR) in healthy, prediabetes, and diabetes cohorts. One hundred three volunteers (50 persons with overt diabetes mellitus, 24 relatives of patients with diabetes, and 29 nondiabetic individuals without a family history of diabetes) completed both FFQ and 7DR. A second FFQ was completed by 100 of these volunteers after 3 months to evaluate its reproducibility. Data were compared by correlation and Bland-Altman analyses. Across the entire group, estimates for gram intakes of nutrients and total energy were associated with wide limits of agreement between FFQ and 7DR (correlation coefficients, 0.23-0.72; P < .02). Compared with 7DR, the FFQ overestimated intakes of saturated fat in the entire group (+6.6 ± 14 g; P < .001) and in persons with overt diabetes mellitus (+7.6 ± 15 g; P < .001) but underestimated protein intake in relatives of patients with diabetes (-16.36 ± 31 g; P = .01). The repeated FFQ revealed variable agreement (correlation coefficients, 0.34-0.72; P < .001) and underestimated (P < .01) macronutrient and total energy intakes, with slightly better performance in persons with overt diabetes mellitus and relatives of patients with diabetes than in nondiabetic individuals without a family history of diabetes. Hence, the FFQ allows measuring intakes of total energy and macronutrients in prediabetes and diabetes cohorts but reveals limitations when assessing dietary composition.

Lower fasting muscle mitochondrial activity relates to hepatic steatosis in humans.

OBJECTIVE: Muscle insulin resistance has been implicated in the development of steatosis and dyslipidemia by changing the partitioning of postprandial substrate fluxes. Also, insulin resistance may be due to reduced mitochondrial function. We examined the association between mitochondrial activity, insulin sensitivity, and steatosis in a larger human population. RESEARCH DESIGN AND METHODS: We analyzed muscle mitochondrial activity from ATP synthase flux (fATP) and ectopic lipids by multinuclei magnetic resonance spectroscopy from 113 volunteers with and without diabetes. Insulin sensitivity was assessed from M values using euglycemic-hyperinsulinemic clamps and/or from oral glucose insulin sensitivity (OGIS) using oral glucose tolerance tests. RESULTS: Muscle fATP correlated negatively with hepatic lipid content and HbA1c. After model adjustment for study effects and other confounders, fATP showed a strong negative correlation with hepatic lipid content and a positive correlation with insulin sensitivity and fasting C-peptide. The negative correlation of muscle fATP with age, HbA1c, and plasma free fatty acids was weakened after adjustment. Body mass, muscle lipid contents, plasma lipoproteins, and triglycerides did not associate with fATP. CONCLUSIONS: The association of impaired muscle mitochondrial activity with hepatic steatosis supports the concept of a close link between altered muscle and liver energy metabolism as early abnormalities promoting insulin resistance.

[Diabetes education in adult diabetic patients]. / Diabetesschulung bei Erwachsenen mit Diabetes.

Diabetes education has gained a critical role in diabetes care. The empowerment of patients aims to actively influence the course of the disease by self-monitoring and treatment modification. Diabetes education has to be made accessible for all patients with the disease. To be able to provide a structured and validated education program adequate personal as well as space, organizational and financial background are required. Besides an increase in knowledge about the disease it has been shown that structured diabetes education is able to improve diabetes outcome measured by parameters like blood glucose, HbA1c, blood pressure and body weight in follow-up evaluations.

A single nucleotide polymorphism associates with the response of muscle ATP synthesis to long-term exercise training in relatives of type 2 diabetic humans.

OBJECTIVE: Myocellular ATP synthesis (fATP) associates with insulin sensitivity in first-degree relatives of subjects with type 2 diabetes. Short-term endurance training can modify their fATP and insulin sensitivity. This study examines the effects of moderate long-term exercise using endurance or resistance training in this cohort. RESEARCH DESIGN AND METHODS: A randomized, parallel-group trial tested 16 glucose-tolerant nonobese relatives (8 subjects in the endurance training group and 8 subjects in the resistance training group) before and after 26 weeks of endurance or resistance training. Exercise performance was assessed from power output and oxygen uptake (VO(2)) during incremental tests and from maximal torque of knee flexors (MaxT(flex)) and extensors (MaxT(ext)) using isokinetic dynamometry. fATP and ectopic lipids were measured with (1)H/(31)P magnetic resonance spectroscopy. RESULTS: Endurance training increased power output and VO(2) by 44 and 30%, respectively (both P < 0.001), whereas resistance training increased MaxT(ext) and MaxT(flex) by 23 and 40%, respectively (both P < 0.001). Across all groups, insulin sensitivity (382 ± 90 vs. 389 ± 40 mL · min(-1) · m(-2)) and ectopic lipid contents were comparable after exercise training. However, 8 of 16 relatives had 26% greater fATP, increasing from 9.5 ± 2.3 to 11.9 ± 2.4 µmol · mL(-1) · m(-1) (P < 0.05). Six of eight responders were carriers of the G/G single nucleotide polymorphism rs540467 of the NDUFB6 gene (P = 0.019), which encodes a subunit of mitochondrial complex I. CONCLUSIONS: Moderate exercise training for 6 months does not necessarily improve insulin sensitivity but may increase ATP synthase flux. Genetic predisposition can modify the individual response of the ATP synthase flux independently of insulin sensitivity.

Postprandial and fasting hepatic glucose fluxes in long-standing type 1 diabetes.

OBJECTIVE: Intravenous insulin infusion partly improves liver glucose fluxes in type 1 diabetes (T1D). This study tests the hypothesis that continuous subcutaneous insulin infusion (CSII) normalizes hepatic glycogen metabolism. RESEARCH DESIGN AND METHODS: T1D with poor glycemic control (T1Dp; HbA(1c): 8.5 ± 0.4%), T1D with improved glycemic control on CSII (T1Di; 7.0 ± 0.3%), and healthy humans (control subjects [CON]; 5.2 ± 0.4%) were studied. Net hepatic glycogen synthesis and glycogenolysis were measured with in vivo (13)C magnetic resonance spectroscopy. Endogenous glucose production (EGP) and gluconeogenesis (GNG) were assessed with [6,6-(2)H(2)]glucose, glycogen phosphorylase (GP) flux, and gluconeogenic fluxes with (2)H(2)O/paracetamol. RESULTS: When compared with CON, net glycogen synthesis was 70% lower in T1Dp (P = 0.038) but not different in T1Di. During fasting, T1Dp had 25 and 42% higher EGP than T1Di (P = 0.004) and CON (P < 0.001; T1Di vs. CON: P = NS). GNG was 74 and 67% higher in T1Dp than in T1Di (P = 0.002) and CON (P = 0.001). In T1Dp, GP flux (7.0 ± 1.6 µmol ⋅ kg(-1) ⋅ min(-1)) was twofold higher than net glycogenolysis, but comparable in T1Di and CON (3.7 ± 0.8 and 4.9 ± 1.0 µmol ⋅ kg(-1) ⋅ min(-1)). Thus T1Dp exhibited glycogen cycling (3.5 ± 2.0 µmol ⋅ kg(-1) ⋅ min(-1)), which accounted for 47% of GP flux. CONCLUSIONS: Poorly controlled T1D not only exhibits augmented fasting gluconeogenesis but also increased glycogen cycling. Intensified subcutaneous insulin treatment restores these abnormalities, indicating that hepatic glucose metabolism is not irreversibly altered even in long-standing T1D.

Short-term exercise training does not stimulate skeletal muscle ATP synthesis in relatives of humans with type 2 diabetes.

OBJECTIVE: We tested the hypothesis that short-term exercise training improves hereditary insulin resistance by stimulating ATP synthesis and investigated associations with gene polymorphisms. RESEARCH DESIGN AND METHODS: We studied 24 nonobese first-degree relatives of type 2 diabetic patients and 12 control subjects at rest and 48 h after three bouts of exercise. In addition to measurements of oxygen uptake and insulin sensitivity (oral glucose tolerance test), ectopic lipids and mitochondrial ATP synthesis were assessed using(1)H and(31)P magnetic resonance spectroscopy, respectively. They were genotyped for polymorphisms in genes regulating mitochondrial function, PPARGC1A (rs8192678) and NDUFB6 (rs540467). RESULTS: Relatives had slightly lower (P = 0.012) insulin sensitivity than control subjects. In control subjects, ATP synthase flux rose by 18% (P = 0.0001), being 23% higher (P = 0.002) than that in relatives after exercise training. Relatives responding to exercise training with increased ATP synthesis (+19%, P = 0.009) showed improved insulin sensitivity (P = 0.009) compared with those whose insulin sensitivity did not improve. A polymorphism in the NDUFB6 gene from respiratory chain complex I related to ATP synthesis (P = 0.02) and insulin sensitivity response to exercise training (P = 0.05). ATP synthase flux correlated with O(2)uptake and insulin sensitivity. CONCLUSIONS: The ability of short-term exercise to stimulate ATP production distinguished individuals with improved insulin sensitivity from those whose insulin sensitivity did not improve. In addition, the NDUFB6 gene polymorphism appeared to modulate this adaptation. This finding suggests that genes involved in mitochondrial function contribute to the response of ATP synthesis to exercise training.