Treatment satisfaction correlated with glycaemic control and burden of diabetes in Swedish adolescents with type 1 diabetes.

AIM: To assess treatment satisfaction and perceived discomfort or pain from the treatment, and potential associations with glycaemic control, type of treatment, perceived burden of diabetes, sex and age, in adolescents with type 1 diabetes. METHODS: A cross-sectional study was performed at one paediatric and at one adult diabetes clinic in Sweden, preceded by a translation of 'Diabetes Treatment Satisfaction Questionnaire (DTSQ) Teen'. Adolescents with type 1 diabetes (15-20 years) participated. The questionnaires 'DTSQ Teen' and 'Check your health' were used. Data on glycosylated haemoglobin (HbA1c), type of treatment, sex and age were collected. RESULTS: One hundred and thirty-eight adolescents (70 females, mean age 17.3, mean HbA1c 64.0 mmol/mol) participated. Treatment satisfaction correlated inversely with HbA1c (r = -.352, P < .001) and with all types of burden of diabetes (r = -.342 to -0.467, P < .001), but did not differ with type of treatment, sex and age. Perceived pain correlated inversely with burden on physical health (r = -.265, P = .002), mental health (r = -.237, P = .006) and quality of life (r = -.246, P = .004) but not with HbA1c, age or burden on social relations. Females perceived more discomfort or pain. CONCLUSION: In Swedish adolescents with type 1 diabetes, treatment satisfaction correlated with both glycaemic control and perceived burden of diabetes.

Catecholamine regulation of local lactate production in vivo in skeletal muscle and adipose tissue: role of -adrenoreceptor subtypes.

CONTEXT: The regulation of lactate production in skeletal muscle (SM) and adipose tissue (AT) is not fully elucidated. OBJECTIVE: Our objective was to investigate the catecholamine-mediated regulation of lactate production and blood flow in SM and AT in healthy, normal-weight subjects by using microdialysis. METHODS: First, lactate levels in SM and AT were measured during an iv norepinephrine infusion (n = 11). Local blood flow was determined with the 133Xe-clearance technique. Second, muscle lactate was measured during hypoglycemia and endogenous epinephrine stimulation (n = 12). Third, SM was perfused with selective beta(1-3)-adrenoreceptor agonists in situ (n = 8). Local blood flow was measured with the ethanol perfusion technique. RESULTS: In response to iv norepinephrine, the fractional release of lactate (difference between tissue and arterial lactate) increased by 40% in SM (P = 0.001), whereas remaining unchanged in AT. Blood flow decreased by 40% in SM (P < 0.005) and increased by 50% in AT (P < 0.05). In response to hypoglycemia, epinephrine increased 10-fold, and the fractional release of lactate in SM doubled (P < 0.0001). The blood flow remained unchanged. The beta2-agonist, terbutaline, caused a marked concentration-dependent increase of muscle lactate and blood flow (P < 0.0001). The beta(1)-agonist, dobutamine, induced a discrete increase of muscle lactate (P < 0.0001), and the blood flow remained unchanged. The beta3-agonist, CPG 12177, did not affect muscle lactate or blood flow. CONCLUSIONS: Catecholamines stimulate lactate production in SM, but not in AT. In SM, the beta2-adrenoreceptor is the most important beta-adrenergic receptor subtype in the regulation of lactate production.

Human skeletal muscle lipolysis is more responsive to epinephrine than to norepinephrine stimulation in vivo.

CONTEXT: Triglyceride (TG) deposits in skeletal muscle (SM) are an important energy reservoir, and increased im TG content is associated with muscle insulin resistance. OBJECTIVE: The objective of the study was to investigate the effect of endogenous catecholamines on TG lipolysis in human SM in vivo. Adipose tissue (AT) was studied for comparison. DESIGN AND MAIN OUTCOME MEASURES: Glycerol levels (index of lipolysis) were measured using microdialysis in the gastrocnemius muscle and abdominal sc adipose tissue during a hyperinsulinemic, hypoglycemic clamp (n = 13) and in response to in situ perfusion of epinephrine and norepinephrine (10(-10) to 10(-5) m) (n = 12). Local tissue blood flow was monitored with the ethanol perfusion technique. SETTING: This was an experimental study. PARTICIPANTS: The study population consisted of healthy subjects. RESULTS: Plasma epinephrine increased 10-fold and plasma norepinephrine 2-fold in response to insulin-induced hypoglycemia. In parallel, the fractional glycerol release (difference between tissue and arterial glycerol) increased 2-fold in both tissues (P < 0.0001). No changes in AT and SM blood flow were registered. When the catecholamines were perfused in situ, tissue glycerol increased significantly at 10(-7) m of either epinephrine and norepinephrine (P < 0.0001) in AT. The maximum stimulation was seen at 10(-6) m norepinephrine (2-fold increase) and 10(-5) m epinephrine (3-fold increase). In SM, tissue glycerol increased at 10(-7) m epinephrine and 10(-6) m norepinephrine, respectively (P < 0.0001); the maximum increase of glycerol values (at 10(-6) m) was 2.5 times for epinephrine and 1.6 times for norepinephrine, respectively (P < 0.01). CONCLUSIONS: The lipolytic activity of SM is increased by endogenous catecholamines in vivo and appears to be more responsive to epinephrine than norepinephrine stimulation.

Improved glucose metabolism after gastric bypass: evolution of the paradigm.

BACKGROUND: Glucose metabolism is improved in patients with type 2 diabetes after Roux-en-Y gastric bypass (RYGB). OBJECTIVES: To quantify the relative contribution of calorie restriction, rerouting of nutrients, and adipose tissue reduction. SETTING: University Hospital. METHODS: Fifteen diabetic patients, (47±9 yr, body mass index 41.3±4.2 kg/m2) were randomized to a 2-week very low-calorie diet (VLCD) regimen or normal diet before RYGB. A euglycemic-hyperinsulinemic clamp, indirect calorimetry, and a standard meal test were performed prediet, postdiet (preoperatively), and 2 weeks and 12 months postoperatively. The primary outcome was whole-body insulin sensitivity (M) measured with the clamp 2 weeks postoperatively. RESULTS: In the VLCD group, after 2 weeks of calorie restriction, M improved (2.9±1.3 to 4.2±1.1 mg/kg/min, P = .005) with no further change at 2 weeks postoperatively. In the normal diet group 2 weeks postoperatively, M was similar to the VLCD group (4.7±1.7 versus 4.2±1.1, P = .61). One year postoperatively, M improved further in both groups. The improvement in insulin-stimulated glucose uptake after VLCD and RYGB was entirely accounted for by nonoxidative glucose disposal (NOGD), whereas weight loss at 1 year postoperatively was associated with an increase in NOGD and glucose oxidation. Postprandial glucose improved after VLCD (P<.05) and even more 2 weeks after RYGB (P<.05) with no further change after 1 year. CONCLUSION: Improved whole-body insulin sensitivity and postprandial glucose response occur early after RYGB. Low calorie intake and rerouting of nutrients contribute through distinct mechanisms. Weight loss contributes by increasing whole-body insulin sensitivity, including glucose oxidation and NOGD. These data suggest that the combination of different mechanisms is what makes RYGB an effective intervention for type 2 diabetes.

Marked reutilization of free fatty acids during activated lipolysis in human skeletal muscle.

Release of glycerol and free fatty acids (FFA) was investigated in human skeletal muscle strips. In the basal state, glycerol and FFA were released at almost equimolar rates (0.3 nmol/ng tissue.90 min). A nonselective beta-adrenoceptor agonist, isoprenaline, caused a concentration-dependent stimulation of glycerol release, whereas FFA release was unaffected. Basal and isoprenaline-induced glycerol release correlated positively with the age of the donors (r = 0.5, P < 0.005) but not with their body mass index (P > or = 0.4). Biochemical experiments with hormone-sensitive lipase (HSL) showed that most enzyme activity was both in the cytosol and mitochondrial fraction and that it constituted the common long and active form of the protein. Electron microscopy studies in rat skeletal muscle using labeled highly specific HSL antibodies verified the cytosolic location of HSL and, furthermore, indicated an accumulation of HSL-adjoining mitochondria. These results suggest that FFA produced in myocytes during catecholamine-induced lipolysis are retained by the muscle and, therefore by inference, reused. It is conceivable that efficient hydrolysis of acylglycerol by HSL located in the cytosol as well as near the mitochondria may facilitate mitochondrial FFA oxidation. In addition, muscle lipolysis activity increases during aging and may be independent of total body fat.

Marked heterogeneity of human skeletal muscle lipolysis at rest.

In this study, variations in lipolysis among different muscle groups were examined by measuring local net glycerol release in vivo in healthy, normal-weight subjects (n = 11) during rested, postabsorptive conditions. Microdialysis of the gastrocnemius, deltoid, and vastus lateralis muscle regions revealed that extracellular glycerol concentrations of these three muscle regions were 84.7 +/- 6.7, 59.7 + 7.3, and 56.4 +/- 7.5 micro mol/l, respectively, and the arterial plasma glycerol concentration was 44.8 +/- 2.3 micro mol/l (P = 0.0003-0.006, gastrocnemius vs. others). Local tissue blood flow, as measured by Xe clearance, did not differ among the regions. Net glycerol release was significantly higher in gastrocnemius muscle than in the two other regions. There were no regional differences in glycerol uptake when studied during glycerol infusion. Gastrocnemius muscle showed a dominance of type 1 fibers (70%), whereas the vastus lateralis muscle had equal distribution of fiber types (P = 0.02). No differences in intramuscular triaclyceride content, perimuscular fat, or the adipocyte-specific protein perilipin were observed among the muscle regions. Triglyceride turnover in the gastrocnemius muscle was 3.3 + 1.4% over 24 h, which is about 10 times more rapid than the turnover rate in subcutaneous adipose tissue (P < 0.01). Thus there were marked differences in lipolytic activity among skeletal muscle groups at rest, possibly reflecting variations in fiber type.

Combined hyperinsulinemia and hyperglycemia, but not hyperinsulinemia alone, suppress human skeletal muscle lipolytic activity in vivo.

Effects of circulating insulin and glucose concentrations on skeletal muscle and adipose tissue lipolytic activity were investigated in 10 type 1 diabetes patients with no endogenous insulin secretion. Microdialysis measurements of interstitial glycerol and determination of fractional glycerol release were carried out during standardized combinations of relative hypoinsulinemia/moderate hyperglycemia (11 mmol/liter), hyperinsulinemia/ normoglycemia (5 mmol/liter), and hyperinsulinemia/moderate hyperglycemia, respectively. Local tissue blood flow rates were measured with the (133)Xe clearance technique. In response to the change from hypo- to hyperinsulinemia, the fractional release of glycerol decreased from 159.6 +/- 17.8 to 85.1 +/- 13.7 micromol/liter (P < 0.0001) in adipose tissue, whereas it remained unchanged in skeletal muscle (44.6 +/- 6.4 vs. 36.0 +/- 7.4 micromol/liter; not significant). When hyperinsulinemia was combined with hyperglycemia, fractional glycerol release was further reduced in adipose tissue (64.5 +/- 12.2 micromol/liter; P < 0.05), and in this situation it was also markedly decreased in skeletal muscle (18.1 +/- 4.8 micromol/liter; P < 0.0001). Skeletal muscle blood flow was unaltered over the respective study periods. Adipose tissue blood flow decreased by 50% in response to hyperinsulinemia (P < 0.0005), but no further change was seen when hyperinsulinemia was combined with hyperglycemia. It is concluded that in patients with type 1 diabetes, insulin does not exert an antilipolytic effect in skeletal muscle during normoglycemia. However, in response to combined hyperinsulinemia and hyperglycemia, the lipolytic activity in skeletal muscle is restrained in a similar way as in adipose tissue. This may be explained by a glucose-mediated potentiation of the antilipolytic effectiveness of insulin.

Treatment of diabetes prior to and after bariatric surgery.

The number of patients undergoing bariatric surgery for morbid obesity is increasing. Type 2 diabetes is common among patients undergoing bariatric surgery. The effect of bariatric surgery on glycemia is profound in patients with diabetes and might vary between different bariatric surgical procedures. Therefore, almost invariably, there is a need to adjust antidiabetic drug dosages in the postoperative period in order to prevent hypoglycemia. Moreover, preoperatively, very low calorie diet protocols are applied in many centers to facilitate surgery by reducing liver volume. Because low caloric intake will increase insulin sensitivity, there is also a need for dose adjustments of glucose-lowering drugs during this period as well. Guidelines for adjustments of antidiabetic treatment before and after bariatric surgery are scarce. In this article, an overview of different bariatric surgical procedures as well as their effects on diabetes are presented. Recommendations on the perioperative antidiabetic treatment are proposed.

Lactate release from adipose tissue and skeletal muscle in vivo: defective insulin regulation in insulin-resistant obese women.

To study the local tissue lactate production in the normal state and its possible disturbances in insulin resistance, rates of lactate release from adipose tissue (AT) and skeletal muscle (SM) were compared postabsorptively and during a hyperinsulinemic euglycemic clamp in 11 healthy nonobese and 11 insulin-resistant obese women. A combination of microdialysis, to measure interstitial lactate, and the 133Xe clearance technique, to determine local blood flow, were used. In the controls, local blood flow increased by 40% in SM (P<0.05) and remained unchanged in AT, whereas the interstitial-plasma difference in lactate doubled in AT (P<0.005) and was unaffected in SM during hyperinsulinemia. In the obese, blood flow and interstitial-plasma difference in lactate remained unchanged in both tissues during hyperinsulinemia. The lactate release (micromol100 g-1min-1) was 1.17+/-0.22 in SM and 0.43+/-0.11 in AT among the controls (P<0.01) and 0.86+/-0.23 in SM and 0.83+/-0.25 in AT among the obese women in the postabsorptive state. During insulin infusion, lactate release in the controls increased to 1.92+/-0.26 in SM (P<0.005) and to 1.14+/-0.22 in AT (P<0.005) but remained unchanged in the obese women. It is concluded that AT and SM are both significant sources of lactate release postabsorptively, and AT is at least as responsive to insulin as SM. The ability to increase lactate release in response to insulin is impaired in AT and SM in insulin-resistant obese women, involving defective insulin regulation of both tissue lactate metabolism and local blood flow.

No apparent suppression by insulin of in vivo skeletal muscle lipolysis in nonobese women.

To investigate the antilipolytic effect of insulin in skeletal muscle and adipose tissue in vivo, the rates of glycerol release from the two tissues were compared in 10 nonobese women during a two-step euglycemic hyperinsulinemic clamp. Tissue interstitial glycerol levels were determined by microdialysis, and tissue blood flow was assessed with the (133)Xe clearance technique. Absolute rates of glycerol release were estimated according to Fick's principle. In both adipose tissue and muscle, glycerol levels decreased significantly already during the low insulin infusion rate. The fractional release of glycerol (difference between interstitial glycerol and arterialized venous plasma glycerol) was reduced by more than one-half in adipose tissue (P < 0.0001) in response to insulin, whereas it remained unaltered in skeletal muscle. Muscle blood flow rates increased by 60% (P < 0.02) during insulin infusion; in adipose tissue, blood flow rates did not change significantly in response to insulin. The basal rate of glycerol release from skeletal muscle amounted to approximately 15% of that from adipose tissue. After insulin infusion, the rate of adipose tissue glycerol release was markedly suppressed, whereas in skeletal muscle the rate of glycerol mobilization did not change significantly in response to insulin. It is concluded that insulin does not inhibit the rate of lipolysis in skeletal muscle of nonobese women.