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Biomedical subjects

M Stumvoll

Publications and source records attributed to M Stumvoll.

At least 91 records · Page 5Linked to original sources
PubMed2000

Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity.

OBJECTIVE: The oral glucose tolerance test (OGTT) has often been used to evaluate apparent insulin release and insulin resistance in various clinical settings. However, because insulin sensitivity and insulin release are interdependent, to what extent they can be predicted from an OGTT is unclear. RESEARCH DESIGN AND METHODS: We studied insulin sensitivity using the euglycemic-hyperinsulinemic clamp and insulin release using the hyperglycemic clamp in 104 nondiabetic volunteers who had also undergone an OGTT. Demographic parameters (BMI, waist-to-hip ratio, age) and plasma glucose and insulin values from the OGTT were subjected to multiple linear regression to predict the metabolic clearance rate (MCR) of glucose, the insulin sensitivity index (ISI), and first-phase (1st PH) and second-phase (2nd PH) insulin release as measured with the respective clamps. RESULTS: The equations predicting MCR and ISI contained BMI, insulin (120 min), and glucose (90 min) and were highly correlated with the measured MCR (r = 0.80, P < 0.00005) and ISI (r = 0.79, P < 0.00005). The equations predicting 1st PH and 2nd PH contained insulin (0 and 30 min) and glucose (30 min) and were also highly correlated with the measured 1st PH (r = 0.78, P < 0.00005) and 2nd PH (r = 0.79, P < 0.00005). The parameters predicted by our equations correlated better with the measured parameters than homeostasis model assessment for secretion and resistance, the delta30-min insulin/delta30-min glucose ratio for secretion and insulin (120 min) for insulin resistance taken from the OGTT. CONCLUSIONS: We thus conclude that predicting insulin sensitivity and insulin release with reasonable accuracy from simple demographic parameters and values obtained during an OGTT is possible. The derived equations should be used in various clinical settings in which the use of clamps or the minimal model would be impractical.

Blood Glucose↗
PubMed1999

Lipolysis in skeletal muscle is rapidly regulated by low physiological doses of insulin.

AIMS/HYPOTHESIS: Both patients with Type II (non-insulin-dependent) diabetes mellitus and normoglycaemic, insulin resistant subjects were shown to have an increased lipid content in skeletal muscle, which correlates negatively with insulin sensitivity. Recently, it was shown that during a hyperinsulinaemic euglycaemic clamp interstitial glycerol was reduced not only in adipose tissue but also in skeletal muscle. To assess whether lipolysis of muscular lipids is also regulated by low physiological concentrations of insulin, we used the microdialysis technique in combination with a 3-step hyperinsulinaemic glucose clamp. METHODS: Nineteen lean, healthy subjects (12 m/7 f) underwent a glucose clamp with various doses of insulin (GC I = 0.1, GC II = 0.25 and GC III = 1.0 mU x kg(-1) x min(-1)). Two double lumen microdialysis catheters each were inserted in the paraumbilical subcutaneous adipose tissue and in skeletal muscle (tibialis anterior) to measure interstitial glycerol concentration (index of lipolysis) and ethanol outflow (index of tissue flow). RESULTS: During the different steps of the glucose clamp, glycerol in adipose tissue was reduced to 81 +/- 7 % (GC I), 55 +/- 8 % (GC II) and 25 +/- 5 % (GC III), respectively, of basal. In contrast, glycerol in skeletal muscle declined to 73 +/- 5 % (GC I) and to 57 +/- 6 % (GC II) but was not further reduced at GC III. Tissue flow was higher in the skeletal muscle and remained unchanged in both compartments throughout the experiment. CONCLUSION/INTERPRETATION: This study confirms the presence of glycerol release in skeletal muscle. Lipolysis in skeletal muscle and adipose tissue are suppressed similarly by minute and physiological increases in insulin but differently by supraphysiological increases. Inadequate suppression of intramuscular lipolysis resulting in increased availability of non-esterified fatty acids, could represent a potential mechanism involved in the pathogenesis of impaired glucose disposal, i. e. insulin resistance, in muscle. [Diabetologia (1999) 42: 1171-1174]

Adipose Tissue↗
PubMed1999

Long term effect of a structured inpatient diabetes teaching and treatment programme in type 2 diabetic patients: influence of mode of follow-up.

Structured diabetes teaching and treatment programmes (STTP) are increasingly offered for patients with diabetes to improve metabolic control. We prospectively studied the long term-effect of STTP on metabolic control and knowledge of diabetes in patients with type 2 diabetes. In addition, differences in the mode of follow-up by a university diabetes centre (UDC) versus general practitioner (GP) were assessed. Of the 64 patients with type 2 diabetes (61 +/- 10 years old, diabetes duration 11 +/- 7 years) included in the study 52 could be reevaluated after 2 years. Of those, 31 were followed up by the UDC and 21 by their GPs who received detailed follow-up instructions from the UDC. In all patients, HbA1c decreased from 9.1 +/- 0.3% before the programme to 8.3 +/- 0.3% 2 years after the programme (P = 0.004), whereas body mass index increased from 28.8 +/- 0.8 to 30.3 +/- 0.9 kg/m2 (P < 0.001). Patients had a significantly better knowledge of diabetes and diet 2 years after the programme. For all parameters tested, none of the changes differed between patients managed by the UDC versus those managed by their GP. However, patients who chose follow-up by the UDC were more obese and had a better knowledge of diabetes. In conclusion, the STTP for patients with type 2 diabetes was effective in improving the long-term glycaemic control and knowledge of diabetes. Moreover, with precise therapeutic goals and follow-up instructions given to patient and GP this improvement was independent of the mode of outpatient follow-up.

Academic Medical Centers↗
PubMed1999

Role of glutamine in human carbohydrate metabolism in kidney and other tissues.

Glutamine is the most abundant amino acid in the human body and is involved in more metabolic processes than any other amino acid. Until recently, the understanding of many aspects of glutamine metabolism was based on animal and in vitro data. However, recent studies using isotopic and balance techniques have greatly advanced the understanding of glutamine metabolism in humans and its role in glucose metabolism in the kidney and other tissues. There is now evidence that in postabsorptive humans, glutamine is an important glucose precursor and makes a significant contribution to the addition of new carbon to the glucose carbon pool. The importance of alanine for gluconeogenesis, viewed in terms of the addition of new carbons, is less than previously assumed. It appears that glutamine is predominantly a renal gluconeogenic substrate, whereas alanine gluconeogenesis is essentially confined to the liver. As shown recently, renal gluconeogenesis contributes 20 to 25% to whole-body glucose production. Moreover, glutamine has been shown not only to stimulate net muscle glycogen storage but also to stimulate gluconeogenesis in normal humans. Finally, in humans with type II diabetes, conversion of glutamine to glucose is increased (more so than that of alanine). The available evidence on the hormonal regulation of glutamine gluconeogenesis in kidney and liver and its alterations under pathological conditions are discussed.

Alanine↗
PubMed1999

Important role of the kidney in human carbohydrate metabolism.

Recent studies using a combination of isotope and balance techniques have shown that, in the postabsorptive state, the human kidney contributes substantially to overall glucose production and consumption. The kidney may contribute as much as the liver to gluconeogenesis and play an important role in the counterregulation of hypoglycemia. Furthermore, increased renal glucose production may contribute to fasting hyperglycemia found in type I and type II diabetes mellitus. Finally, loss of renal tissue as a consumer of glucose could explain the insulin resistance of uremia. We hypothesize that the human kidney may play a more important role in human carbohydrate metabolism than previously appreciated.

Carbohydrate Metabolism↗
PubMed1999

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Journal Article↗
PubMed1998

Abnormal renal and hepatic glucose metabolism in type 2 diabetes mellitus.

Release of glucose by liver and kidney are both increased in diabetic animals. Although the overall release of glucose into the circulation is increased in humans with diabetes, excessive release of glucose by either their liver or kidney has not as yet been demonstrated. The present experiments were therefore undertaken to assess the relative contributions of hepatic and renal glucose release to the excessive glucose release found in type 2 diabetes. Using a combination of isotopic and balance techniques to determine total systemic glucose release and renal glucose release in postabsorptive type 2 diabetic subjects and age-weight-matched nondiabetic volunteers, their hepatic glucose release was then calculated as the difference between total systemic glucose release and renal glucose release. Renal glucose release was increased nearly 300% in diabetic subjects (321+/-36 vs. 125+/-15 micromol/min, P < 0.001). Hepatic glucose release was increased approximately 30% (P = 0.03), but increments in hepatic and renal glucose release were comparable (2.60+/-0.70 vs. 2.21+/-0.32, micromol.kg-1.min-1, respectively, P = 0.26). Renal glucose uptake was markedly increased in diabetic subjects (353+/-48 vs. 103+/-10 micromol/min, P < 0.001), resulting in net renal glucose uptake in the diabetic subjects (92+/-50 micromol/ min) versus a net output in the nondiabetic subjects (21+/-14 micromol/min, P = 0.043). Renal glucose uptake was inversely correlated with renal FFA uptake (r = -0.51, P < 0.01), which was reduced by approximately 60% in diabetic subjects (10. 9+/-2.7 vs. 27.0+/-3.3 micromol/min, P < 0.002). We conclude that in type 2 diabetes, both liver and kidney contribute to glucose overproduction and that renal glucose uptake is markedly increased. The latter may suppress renal FFA uptake via a glucose-fatty acid cycle and explain the accumulation of glycogen commonly found in the diabetic kidney.

3-Hydroxybutyric Acid↗
PubMed1998

[The human kidney as an important producer of glucose].

BACKGROUND: According to current textbook knowledge the liver is the exclusive site of glucose production in postabsorptive humans. Although many animal and in-vitro data have documented that the kidney is capable of gluconeogenesis, production of glucose by the human kidney has been regarded as negligible to date. This traditional perception is based on methodologically inadequate net balance studies, which other than after a prolonged fast or during metabolic acidosis showed no significant net renal glucose release. STUDIES: Recent tracer studies, however, showing a renal glucose production accounting for 25% of systemic glucose production, have refuted this view. glucose production by the human kidney is stimulated by epinephrine and inhibited by insulin. Glucagon stimulates hepatic but not renal glucose production. The most important renal gluconeogenic precursors are lactate, glutamine and glycerol. The implications of these recent findings on the understanding of the physiology and pathophysiology of human glucose metabolism are discussed. CONCLUSION: Magnitude and regulation of renal glucose production have important consequences for the intermediary metabolism, counterregulation of hypoglycemia, glucose metabolism of uremia and the pathophysiology of type I and type II diabetes.

Animals↗
PubMed1998

Effects of glucagon on renal and hepatic glutamine gluconeogenesis in normal postabsorptive humans.

Glutamine is an important gluconeogenic amino acid in postabsorptive humans. To assess the effect of glucagon on renal and hepatic glutamine gluconeogenesis, we infused six normal healthy postabsorptive subjects with glucagon at a rate chosen to produce circulating glucagon concentrations found during hypoglycemia and, using a combination of isotopic and net balance techniques, determined the systemic, renal, and hepatic glucose release and renal and hepatic production of glucose from glutamine. Infusion of glucagon increased systemic and hepatic glucose release (both P < .02), but had no effect on renal glucose release (P = .26). Systemic and hepatic glutamine gluconeogenesis increased from 0.45 +/- 0.3 and 0.11 +/- 0.02 micromol x kg(-1) x min(-1), respectively, to 0.61 +/- 0.04 (P = .002) and 0.31 +/- 0.03 micromol x kg(-1) x min(-1) (P = .001), respectively, whereas renal glutamine gluconeogenesis was unchanged (from 0.33 +/- 0.03 to 0.30 +/- 0.04 micromol x kg(-1) x min(-1), P = .20). The hepatic contribution to systemic glutamine gluconeogenesis increased from 25.2% +/- 6.2% to 51.6% +/- 5.5% (P = .002), while that of the kidney decreased from 74.8% +/- 6.2% to 48.4% +/- 5.5% (P = .003). Glucagon had no effect on the renal net balance, fractional extraction, or uptake and release of either glucose or glutamine. We thus conclude that glucagon stimulates glutamine gluconeogenesis in normal postabsorptive humans, predominantly due to an increase in hepatic glutamine conversion to glucose. Thus, under certain conditions such as counterregulation of hypoglycemia, the liver may be an important site of glutamine gluconeogenesis.

Adult↗
PubMed1998

Diabetes teaching program improves glycemic control and preserves perception of hypoglycemia.

Improvement of HbA1c is frequently accompanied by deteriorating awareness of hypoglycemia. We studied the effect of improved metabolic control on hypoglycemia perception in 33 type 1 diabetic patients during 3 months after an inpatient diabetes education program of 5 days. Patients were grouped according to the presence (H, n = 11) or the absence (N, n = 22) of a history of repeated severe hypoglycemia. To measure awareness of blood glucose (BG) and hypoglycemia, we calculated their accuracy of BG perception (error grid analysis) and sensitivity for BG levels < 3.9 mmol/l, respectively, during the first (I) and second (II) period of the 3 months using the method of BG estimation. HbA1c decreased from 8.0 +/- 0.3% before to 7.1 +/- 0.2% 3 months after the program (P < 0.001) with no difference between H and N. Neither accuracy of BG perception (40.6 +/- 3.8 (I) versus 43.6 +/- 4.1% (II), P = 0.25) nor sensitivity for low BG levels (49.1 +/- 4.2 (I) versus 54.9 +/- 4.9% (II), P = 0.12) changed significantly. Group H had a lower overall accuracy of BG estimation (P = 0.048) and a lower overall sensitivity for detecting BG levels < 3.9 mmol/l (P = 0.03) than group N. Group H was able to improve accuracy of BG estimation (H: 24.8 +/- 6.2 (I) versus 36.9 +/- 8.3% (II), P = 0.04) while group N was not (48.5 +/- 3.9 (I) versus 46.9 +/- 4.6% (II), P = 0.5). In conclusion, improvement of metabolic control after intensive diabetes education had no adverse effect on the perception of low BG levels. On the contrary, patients with a history of severe hypoglycemia improved their awareness of BG.

Adult↗
PubMed1998

Evidence for inhibition of leptin secretion by catecholamines in man.

The regulation of leptin secretion is complex and not entirely understood in humans. Insulin has been shown to stimulate leptin secretion in humans, whereas in vitro data suggest that catecholamines inhibit leptin secretion. The present studies were therefore undertaken to examine the leptin response to hyperinsulinemia in the presence and absence of elevated plasma levels of endogenous catecholamines in humans. Leptin concentrations were determined during both a euglycemic and hypoglycemic hyperinsulinemic clamp study in 10 normal and 10 type I diabetic subjects. Serum leptin increased during the hyperinsulinemic euglycemic clamp in normal (from 6.1 +/- 0.9 to 7.2 +/- 1.1 ng/dl, p = 0.003) and diabetic subjects (from 6.2 +/- 1.4 to 7.8 +/- 1.8 ng/dl, p = 0.001). During hyperinsulinemic hypoglycemia leptin concentrations increased significantly in type 1 diabetic patients (from 5.6 +/- 1.1 to 7.6 +/- 1.7 ng/dl, p = 0.003) but remained unaltered in normals (from 5.5 +/- 0.7 to 5.7 +/- 0.9 ng/dl, p = 0.7). During hypoglycemia in all subjects the increase in leptin was negatively correlated with the increase in epinephrine (r = 0.60, p = 0.005) and positively with the decrease in free fatty acids (r = 0.71, p = 0.003). In conclusion our results indicate that catecholamines play a suppressive role in the regulation of leptin secretion.

Adult↗
PubMed1998

Human kidney and liver gluconeogenesis: evidence for organ substrate selectivity.

To assess the contribution of the human kidney to gluconeogenesis (GN) and its role in conversion of glutamine and alanine to glucose, we used a combination of isotopic and organ balance techniques in nine normal postabsorptive volunteers and measured both overall and renal incorporation of these precursors into glucose before and after infusion of epinephrine. In the postabsorptive basal state, renal incorporation of glutamine (27 +/- 2 mumol/min) and alanine (2.1 +/- 0.5 mumol/min) into glucose accounted for 72.8 +/- 3.3 and 3.9 +/- 0.5% of their overall incorporation into glucose (37 +/- 2 and 51 +/- 6 mumol/min, respectively) and 19.0 +/- 3.5 and 1.4 +/- 0.2%, respectively, of overall renal glucose release. Infusion of epinephrine, which increased systemic and renal glucose release more than twofold (P < 0.001), increased overall glutamine and alanine incorporation into glucose (both P < 0.001) and increased renal GN from glutamine (P < 0.001) but not from alanine (P = 0.15). Renal glutamine GN now accounted for 90.3 +/- 4.0% of overall glutamine GN (P = 0.01 vs. basal), whereas renal alanine GN still accounted for only 4.8 +/- 1.7% of overall alanine GN (P = 0.36 vs. basal). With the assumption that kidney and liver are the only gluconeogenic organs in humans, these results indicate that glutamine GN occurs primarily in kidney, whereas alanine GN occurs almost exclusively in liver. Isotopic studies of glutamine and alanine incorporation into plasma glucose may provide a selective, noninvasive method to assess hepatic and renal GN.

Adult↗
PubMed1998

Effect of hypoglycemia on beta-adrenergic sensitivity in normal and type 1 diabetic subjects.

OBJECTIVE: The purpose of this study was to assess the potential role of reduced tissue sensitivity to catecholamines in the pathogenesis of hypoglycemia unawareness in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: The effect of a single episode of hypoglycemia on beta-adrenergic sensitivity was studied in 10 type 1 diabetic patients with apparently normal awareness of hypoglycemia (age 29 +/- 5 years, diabetes duration 13 +/- 8 years, HbA1c 7.3 +/- 0.9%) and 10 age-matched healthy control subjects. Beta-adrenergic sensitivity was measured with the isoproterenol test after a hyperinsulinemic euglycemic clamp and after a hyperinsulinemic hypoglycemic clamp. Beta-adrenergic sensitivity was expressed as the dose of intravenous isoproterenol that increased the heart rate by 25 beats/min (IC25). RESULTS: During hypoglycemia, diabetic subjects had an impaired plasma epinephrine response compared with that of the control subjects (16.7 +/- 5.0 vs. 40.1 +/- 6.8 ng/ml, P = 0.02). In control subjects, the IC25 was lower after hypoglycemia than after euglycemia (0.83 +/- 0.22 vs. 1.13 +/- 0.21 microg, P = 0.02) indicating an increase in beta-adrenergic sensitivity. In diabetic subjects, on the other hand, the IC25 was greater after hypoglycemia than after euglycemia (1.00 +/- 0.26 vs. 0.65 +/- 0.14 microg, P = 0.04), indicating a decrease in beta-adrenergic sensitivity. CONCLUSIONS: In normal subjects, a single episode of hypoglycemia increases beta-adrenergic sensitivity. In diabetic subjects, in contrast, hypoglycemia reduces beta-adrenergic sensitivity. These results provide evidence that in type 1 diabetic patients, some maladaptation of tissue sensitivity to catecholamines contributes to the development of hypoglycemia unawareness. A unifying hypothesis is presented for the pathogenesis of hypoglycemia unawareness in type 1 diabetic patients incorporating the concepts of both a reduced catecholamine response and reduced adrenergic sensitivity

Adrenergic beta-Agonists↗