Biomedical subjects

R A Rizza

Publications and source records attributed to R A Rizza.

At least 37 records · Page 2Linked to original sources

PubMed2000

Towards an optimal model for community-based diabetes care: design and baseline data from the Mayo Health System Diabetes Translation Project.

The objective of the Mayo Health System Diabetes Translation Project is to assess the impact of three different models of care on the overall quality of diabetes care in the community. The unit of study is the primary care practice with a different model of care implemented at each of three sites. The design incorporates a comparison of a diabetes guideline implementation team initiative (Practice model A), a guideline initiative combined with clinical use of a Diabetes Electronic Management System (DEMS) by primary care providers (Practice model B) and a guideline initiative combined with DEMS utilization combined with electronic review of DEMS patient encounters by an endocrinologist (Practice model C). Administrative data sets were used to define the patient population at each practice. Patients were designated as new, attending or non-attending based on their pattern of visits over the preceding 12 months. A random sample of 200 charts from attending patients at each site was audited at baseline for diabetes-related process and outcome measures. This audit will be repeated yearly during the 2 years of the project. Baseline data revealed significant differences across sites in adherence to certain key indicators of the quality of diabetes care including: frequency of documentation of eye examinations (19, 39 and 37% for sites A, B and C, respectively), haemoglobin A1c monitoring (64, 89 and 77%) and microalbumin monitoring (3, 15 and 6%). The interventions being assessed in this study include traditional (diabetes education; guideline implementation) and modern (DEMS; telemedicine specialist review) methods for improving the quality of diabetes care. In spite of variation in baseline quality indicators, the setting and design should lead to broad applicability of the results and help determine an optimal model of diabetes care in the community.

Community Health Services↗

PubMed2000

Pramlintide, an amylin analog, selectively delays gastric emptying: potential role of vagal inhibition.

The amylin analog pramlintide delays gastric emptying in type I diabetics. The effects of multiple doses of pramlintide and the mechanism of action in non-amylin-deficient humans are unknown. We investigated the effects of pramlintide on gastrointestinal and colonic transit and on the plasma pancreatic polypeptide response to the meal in a parallel-group dose-response study with subjects randomized to placebo, or 30 or 60 microg (tid, sc) of pramlintide. Pramlintide delayed gastric emptying [half-time (t(1/2)): 112 min (SE 8.7 min), 169 min (SE 12 min), or 177 min (SE 25 min) after placebo or 30- or 60-microg pramlintide treatment, respectively; P = 0.033]. Pramlintide did not significantly affect small bowel or colonic transit. Pancreatic polypeptide concentrations in the first postprandial hour were lower with pramlintide than with placebo (P<0.01 for drug effect). An inverse correlation was observed between mean pancreatic polypeptide concentrations in the first postprandial hour and gastric emptying t(1/2) [Spearman correlation coefficient (R(s)) = 0.48; P = 0.044]. Pramlintide at 30 and 60 microg delays gastric emptying in healthy humans without affecting small bowel or colonic transit. Vagal inhibition is a potential mechanism of the effects of pramlintide on gastric emptying.

Adult↗

PubMed2000

Lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetes mellitus.

We tested the hypothesis that a lack of suppression of glucagon causes postprandial hyperglycemia in subjects with type 2 diabetes. Nine diabetic subjects ingested 50 g glucose on two occasions. On both occasions, somatostatin was infused at a rate of 4.3 nmol/kg x min, and insulin was infused in a diabetic insulin profile. On one occasion, glucagon was also infused at a rate of 1.25 ng/kg x min to maintain portal glucagon concentrations constant (nonsuppressed study day). On the other occasion, glucagon infusion was delayed by 2 h to create a transient decrease in glucagon (suppressed study day). Glucagon concentrations on the suppressed study day fell to about 70 ng/L during the first 2 h, rising thereafter to approximately 120 ng/L. In contrast, glucagon concentrations on the nonsuppressed study day remained constant at about 120 ng/L throughout. The decrease in glucagon resulted in substantially lower (P < 0.001) glucose concentrations on the suppressed compared with the nonsuppressed study days (9.2+/-0.7 vs. 10.9+/-0.8 mmol/L) and a lower (P < 0.001) rate of release of [14C]glucose from glycogen (labeled by infusing [1-14C]galactose). On the other hand, flux through the hepatic UDP-glucose pool (and, by implication, glycogen synthesis), measured using the acetaminophen glucuronide method, did not differ on the two occasions. We conclude that lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetes at least in part by accelerating glycogenolysis. These data suggest that agents that antagonize glucagon action or secretion are likely to be of value in the treatment of patients with type 2 diabetes.

Blood Glucose↗

PubMed2000

Prandial glucose effectiveness and fasting gluconeogenesis in insulin-resistant first-degree relatives of patients with type 2 diabetes.

Impaired glucose effectiveness (i.e., a diminished ability of glucose per se to facilitate its own metabolism), increased gluconeogenesis, and endogenous glucose release are, together with insulin resistance and beta-cell abnormalities, established features of type 2 diabetes. To explore aspects of the pathophysiology behind type 2 diabetes, we assessed in a group of healthy people prone to develop type 2 diabetes (n = 23), namely first-degree relatives of type 2 diabetic patients (FDR), 1) endogenous glucose release and fasting gluconeogenesis measured using the 2H2O technique and 2) glucose effectiveness. The FDR group was insulin resistant when compared with an age-, sex-, and BMI-matched control group without a family history of type 2 diabetes (n = 14) (M value, clamp: 6.07 +/- 0.48 vs. 8.06 +/- 0.69 mg x kg(-1) lean body weight (lbw) x min(-1); P = 0.02). Fasting rates of gluconeogenesis (1.28 +/- 0.06 vs. 1.41 +/- 0.07 mg x kg(-1) lbw x min(-1); FDR vs. control subjects, P = 0.18) did not differ in the two groups and accounted for 53 +/- 2 and 60 +/- 3% of total endogenous glucose release. Glucose effectiveness was examined using a combined somatostatin and insulin infusion (0.17 vs. 0.14 mU x kg(-1) x min(-1), FDR vs. control subjects), the latter replacing serum insulin at near baseline levels. In addition, a 360-min labeled glucose infusion was given to simulate a prandial glucose profile. After glucose infusion, the integrated plasma glucose response above baseline (1,817 +/- 94 vs. 1,789 +/- 141 mmol/l per 6 h), the ability of glucose to simulate its own uptake (1.50 +/- 0.13 vs. 1.32 +/- 0.16 ml x kg(-1) lbw x min(-1)), and the ability of glucose per se to suppress endogenous glucose release did not differ between the FDR and control group. In conclusion, in contrast to overt type 2 diabetic patients, healthy people at high risk of developing type 2 diabetes are characterized by normal glucose effectiveness at near-basal insulinemia and normal fasting rates of gluconeogenesis.

Adult↗

PubMed2000

Effects of type 2 diabetes on the ability of insulin and glucose to regulate splanchnic and muscle glucose metabolism: evidence for a defect in hepatic glucokinase activity.

Insulin-induced stimulation of muscle glucose uptake (MGU) is impaired in people with type 2 diabetes. To determine whether insulin-induced stimulation of splanchnic glucose uptake (SGU) is also impaired, we simultaneously measured leg glucose uptake (LGU) and SGU in 14 nondiabetic subjects and 16 subjects with type 2 diabetes using a combined organ catheterization-tracer infusion technique. Glucose was clamped at approximately 9.3 mmol/l, while insulin concentrations were maintained at approximately 72 pmol/l (low) and approximately 150 pmol/l (high) for 3 h each. Endogenous hormone secretion was inhibited with somatostatin. Total body glucose disappearance was lower (P < 0.01) and glucose production higher (P < 0.01) during both insulin infusions in the diabetic compared with the nondiabetic subjects, indicating insulin resistance. Splanchnic glucose production was higher (P < 0.05) in the diabetic subjects during the low but not the high insulin infusion. SGU was slightly lower in the diabetic than in the nondiabetic subjects during the low insulin infusion and 50-60% lower (P < 0.05) during the high insulin infusion. LGU (P < 0.001), but not SGU, was inversely correlated with the degree of visceral adiposity. The contribution of the indirect pathway to hepatic glycogen synthesis did not differ in the diabetic and nondiabetic subjects. In contrast, both flux through the UDP-glucose pool (P < 0.05) and the contribution of the direct pathway to glycogen synthesis (P < 0.01) were lower in the diabetic than in the nondiabetic subjects, indicating decreased uptake and/or phosphorylation of extracellular glucose. On the other hand, glycogenolysis was equally suppressed in both groups. In summary, type 2 diabetes impairs the ability of insulin to stimulate both MGU and SGU. The defect appears to reside at a proximal (e.g., glucokinase) metabolic step and is not related to the degree of visceral adiposity. These data suggest that impaired hepatic glucose uptake as well as MGU contribute to hyperglycemia in people with type 2 diabetes.

Blood Glucose↗

PubMed2000

Effect of glucagon-like peptide 1(7-36) amide on glucose effectiveness and insulin action in people with type 2 diabetes.

Although it is well established that glucagon-like peptide 1(7-36) amide (GLP-1) is a potent stimulator of insulin secretion, its effects on insulin action and glucose effectiveness are less clear. To determine whether GLP-1 increases insulin action and glucose effectiveness, subjects with type 2 diabetes were studied on two occasions. Insulin was infused during the night on both occasions to ensure that baseline glucose concentrations were comparable. On the morning of study, either GLP-1 (1.2 pmol x kg(-1) x min(-1)) or saline were infused along with somatostatin and replacement amounts of glucagon. Glucose also was infused in a pattern mimicking that typically observed after a carbohydrate meal. Insulin concentrations were either kept constant at basal levels (n = 6) or varied so as to create a prandial insulin profile (n = 6). The increase in glucose concentration was virtually identical on the GLP-1 and saline study days during both the basal (1.21 +/- 0.15 vs. 1.32 +/- 0.19 mol/l per 6 h) and prandial (0.56 +/- 0.14 vs. 0.56 +/- 0.10 mol/l per 6 h) insulin infusions. During both the basal and prandial insulin infusions, glucose disappearance promptly increased after initiation of the glucose infusion to rates that did not differ on the GLP-1 and saline study days. Suppression of endogenous glucose production also was comparable on the GLP-1 and saline study days during both the basal (-2.7 +/- 0.3 vs. -3.1 +/- 0.2 micromol/kg) and prandial (-3.1 +/- 0.4 vs. -3.0 +/- 0.6 pmol/kg) insulin infusions. We conclude that when insulin and glucagon concentrations are matched, GLP-1 has negligible effects on either insulin action or glucose effectiveness in people with type 2 diabetes. These data strongly support the concept that GLP-1 improves glycemic control in people with type 2 diabetes by increasing insulin secretion, by inhibiting glucagon secretion, and by delaying gastric emptying rather than by altering extrapancreatic glucose metabolism.

Blood Glucose↗

PubMed2000

Pancreas transplantation for the prevention of diabetic nephropathy.

Diabetic nephropathy is the leading cause of kidney failure in the United States. Poor glycemic control, hypertension, and smoking have been implicated as risk factors for the development and progression of diabetic nephropathy in patients with type 1 diabetes mellitus. Improved medical therapy including angiotensin-converting enzyme inhibitors and tight glycemic control with use of intensive insulin therapy have been shown to reduce the progression of diabetic nephropathy substantially based on albumin excretion rates. Despite these improvements in medical management, many patients still experience progression from early diabetic nephropathy to end-stage renal disease. Successful pancreas transplantation leads to normal glycemic control in patients with type 1 diabetes, but historically it has generally been limited to patients with both kidney failure and diabetes. In this review of the current treatment of diabetic nephropathy, we examine the potential role of preemptive pancreas transplantation in patients with diabetic nephropathy.

Albuminuria↗

PubMed2000

Controlling blood glucose levels in patients with type 2 diabetes mellitus. An evidence-based policy statement by the American Academy of Family Physicians and American Diabetes Association.

OBJECTIVE: To review evidence about the benefit of intensive glycemic control for patients with type 2 diabetes and to develop practice recommendations. PARTICIPANTS: A 9-member panel composed of family physicians, general internists, endocrinologists, and a practice guidelines methodologist was assembled by the American Academy of Family Physicians, the American Diabetes Association, and the American College of Physicians. EVIDENCE: Admissible evidence included published randomized controlled trials and observational studies regarding the effects of glycemic control on microvascular and macrovascular complications and on adverse effects. We followed systematic search and data abstraction procedures. Greater weight was given to clinical trials and to evidence about health outcomes. CONSENSUS PROCESS: Interpretations of evidence and approval of documents were finalized by unanimous vote, with recommendations linked to evidence and not expert opinion. The full report was prepared by the chair and 2 panel members, representing each of the 3 organizations. The initial draft underwent external review by 14 diabetologists and family physicians and changes consistent with the evidence were incorporated. CONCLUSIONS: The evidence demonstrates that the risk of microvascular and neuropathic complications is reduced by lowering glucose concentrations. Whether glycemic control affects macrovascular outcomes is less clear. The potential benefits of glycemic control must be balanced against factors that either preempt benefits (eg, limited life expectancy, comorbid disease) or increase risk (eg, severe hypoglycemia). The magnitude of benefit is a function of individual clinical variables (eg, baseline glycated hemoglobin level, presence of preexisting microvascular disease). Appropriate targets for treatment should be determined by considering these factors, patients' risk profiles, and personal preferences.

Aged↗

PubMed2000

Androgen effect on insulin action and glucose metabolism.

Our understanding of the effect of androgens on insulin action and glucose metabolism is incomplete. Data derive from several different models and methods, and the limitations of each must be considered. Results suggest that in humans, low-dose testosterone (replacement dosages) may increase insulin action; high-dose testosterone (supplemental or pharmacologic dosages) decreases insulin action; and dehydroepiandrosterone appears to have no effect.

Androgens↗

PubMed1999

Insulin action during variable hyperglycemic-hyperinsulinemic infusions in hyperandrogenic anovulatory patients and healthy women.

OBJECTIVE: To determine whether 3-month GnRH analogue (GnRH-a) administration to hyperandrogenic anovulatory patients and healthy women affects glucose utilization or endogenous glucose production (EGP) in the postabsorptive state and during variable hyperglycemic-hyperinsulinemic infusions. DESIGN: Prospective, nonrandomized study. SETTING: Academic research environment. PATIENT(S): Twelve hyperandrogenic anovulatory patients and 11 healthy women matched by body mass index and waist to hip circumference ratio. INTERVENTION(S): Variable hyperglycemic-hyperinsulinemic infusions replicated physiological increases in circulating glucose and insulin levels before and after 3-month GnRH-a administration. MAIN OUTCOME MEASURE(S): Glucose utilization and EGP. RESULT(S): In the postabsorptive state, plasma glucose and insulin levels, glucose utilization, and EGP were similar in hyperandrogenic patients and healthy women. During variable hyperglycemic-hyperinsulinemic infusions, glucose use increased and EGP decreased to similar degrees in both groups of women. Three-month GnRH-a administration to hyperandrogenic patients and healthy women did not affect plasma glucose and insulin levels, glucose utilization and EGP in the postabsorptive state, or glucose utilization and EGP during variable hyperglycemic-hyperinsulinemic infusions. CONCLUSION(S): Glucose use and EGP in the postabsorptive state and during variable hyperglycemic-hyperinsulinemic infusions are similar in hyperandrogenic anovulatory patients and healthy women of similar body fat distribution and are unaffected by 3-month GnRH-a administration.

Adolescent↗

PubMed1999

Attenuated in vitro coronary arteriolar vasorelaxation to insulin-like growth factor I in experimental hypercholesterolemia.

Insulin and insulin-like growth factor (IGF) 1 affect coronary vasoactivity. Experimental hypercholesterolemia is associated with coronary atherogenesis and altered vasomotor regulation. Because the IGF axis is altered during atherogenesis, we postulated that experimental hypercholesterolemia is associated with an altered coronary vasoactive response to IGF-1 in vitro. Coronary arteries and arterioles from pigs fed either a normal or high-cholesterol diet for 10 weeks were contracted with endothelin-1 and relaxed with cumulative concentrations of insulin or IGF-1 (10(-12) to 10(-7) mol/L). Control arterioles were also incubated with the nitric oxide synthase inhibitor 10(-4) mol/L N(G)-monomethyl-L-arginine (L-NMMA) or the potassium channel blocker 10(-2) mol/L tetraethylammonium (TEA), contracted with endothelin-1, and relaxed with insulin or IGF-1. Experimental hypercholesterolemia (1) increased serum cholesterol (9.5+/-1.0 versus 1.9+/-0.08 mmol/L; P<0.0001), (2) caused coronary arterial and arteriolar endothelial dysfunction in vitro (attenuated vasorelaxation to bradykinin), (3) did not alter the epicardial response to either insulin (P=0.80) or IGF-1 (P=0.12), and (4) significantly attenuated the arteriolar response to IGF-1 (maximal relaxation of 79+/-6% versus 42+/-8%; P=0.01) but not insulin (43+/-6% versus 53+/-7%; P=0.99). Control arteriolar vasorelaxation to IGF-1 was attenuated by both L-NMMA (P<0.001) and TEA (P=0.01), whereas only L-NMMA attenuated insulin (P<0.001). Staining for IGF-1 and IGF binding protein 2 was increased (P<0.05) in arterioles of cholesterol-fed pigs. IGF-1 and insulin are therefore coronary arteriolar vasorelaxants through different mechanisms. Experimental hypercholesterolemia is associated with resistance to the coronary arteriolar vasorelaxing effects of IGF-1 but not insulin, in conjunction with increased ligand and binding-protein expression. The IGF axis may contribute to the altered coronary vasoactivity in hypercholesterolemia.

Animals↗

PubMed1999

Effect of overnight restoration of euglycemia on glucose effectiveness in type 2 diabetes mellitus.

The ability of glucose to stimulate its own uptake and suppress its own release is impaired in type 2 diabetes. To determine whether glucose effectiveness is improved by short term euglycemia, 10 type 2 diabetic subjects were studied on 2 occasions. Insulin was infused throughout the night to maintain euglycemia (approximately 5 mmol/L), or glucose was permitted to remain at ambient hyperglycemic levels (approximately 10 mmol/L) until the following morning when euglycemia was achieved with a variable insulin infusion. A prandial glucose infusion (containing 35 g glucose) was started at 1000 h, and the variable insulin infusion was replaced by a constant infusion of insulin (0.25 mU/ kg x min), somatostatin (60 ng/kg x min), glucagon (0.65 ng/kg x min), and GH (3 ng/kg x min) to maintain hormone concentrations at constant basal levels. Although nocturnal glucose concentrations were (by design) higher (P<0.01) on the hyperglycemic than on the euglycemic study day (10.1+/-0.2 vs. 5.4+/-0.1 mmol/L), glucose concentrations did not differ either before (4.9+/-0.1 vs. 4.9+/-0.1 mmol/L) or during the prandial glucose infusion (peak, 11.1+/-0.5 vs. 11.3+/-0.5 mmol/L; incremental area, 1390+/-254 vs. 1409+/-196 mmol/L x 6 h). Furthermore, glucose-induced stimulation of glucose disappearance (2068+/-218 vs. 1957+/-244 micromol/kg x 6 h) and suppression of glucose production (-2253+/-378 vs. -2124+/-257 micromol/kg x 6 h) did not differ. Thus, restoration of euglycemia by means of an overnight insulin infusion does not alter glucose effectiveness in people with type 2 diabetes.

Blood Glucose↗

PubMed1998

Effects of glucagon on postprandial carbohydrate metabolism in nondiabetic humans.

The present experiments sought to determine whether glucagon concentrations mimicking those observed in people with diabetes mellitus alter postprandial carbohydrate metabolism in nondiabetic humans. We measured the gastric emptying of solids and liquids, the systemic rate of appearance of ingested glucose, and endogenous glucose production either when postprandial suppression of glucagon was prevented by infusing glucagon at a rate of 0.65 ng/kg/min, when postprandial glucagon concentrations were elevated by infusing glucagon at a rate of 3.0 ng/kg/min, or when postprandial suppression of glucagon was permitted by infusion of saline. Despite marked differences in glucagon concentrations, postprandial glucose and insulin concentrations did not differ on any occasion. Although gastric emptying of liquids and solids was comparable on all three occasions, the high-dose, but not the low-dose, glucagon infusion caused a slight delay in the systemic appearance of ingested glucose and a significant decrease (P < .01) in postprandial D-xylose concentrations, suggesting a delay in carbohydrate absorption. However, this was offset by an increase (P < .05) in endogenous glucose production, resulting in no difference in postprandial glucose appearance. We conclude that in the absence of insulin deficiency, neither a lack of suppression of glucagon nor an elevation of glucagon to levels encountered in uncontrolled diabetes mellitus cause postprandial hyperglycemia in nondiabetic humans.

Blood Glucose↗

PubMed1998

Acute postprandial gastrointestinal and metabolic effects of wheat amylase inhibitor (WAI) in normal, obese, and diabetic humans.

Amylase inhibition has gastrointestinal and metabolic effects that may aid in the treatment of diabetes and obesity. We tested whether 4 g of a commercially available wheat amylase inhibitor (WAI) affected postprandial carbohydrate (CHO) absorption and plasma glucose or hormones. Twelve persons (four lean and four obese nondiabetics and four obese type II diabetics) were studied on 2 separate days. After eating a weight maintenance diet (55% CHO, 20% protein, and 25% fat, as percentage of calories) for 3 days, subjects ate a breakfast containing 650 kcal, the same proportion of nutrients as calories, and in random order, either WAI or no WAI. Breath H2 and plasma glucose and hormones were measured every 15 and 30 min, respectively, for 7 h. WAI decreased the delta peak postprandial plasma glucose concentrations in 10 of 12 subjects (p < 0.05) and increased the breath H2 levels in 11 (p = 0.02); the increases in breath H2 were small, generally <20 ppm. No subject experienced a change in stools, diarrhea, or bloating. In response to WAI, gastric inhibitory peptide decreased (p < 0.05), peptide YY increased (p < 0.05), and there was a trend toward increased human pancreatic polypeptide (p = 0.07). Although WAI delays CHO absorption and reduces peak postprandial plasma glucose concentrations, overall CHO malabsorption is minimal (as reflected by breath hydrogen and hormones) and without symptoms. It, therefore, may be useful in treating type II diabetes mellitus.

Adult↗

PubMed1998

Insulin and insulin-like growth factor-I cause coronary vasorelaxation in vitro.

Insulin and insulin-like growth factor-I (IGF-I) may play a role in the modulation of coronary artery tone, yet there are few data regarding their vasoactive effects on the coronary vascular bed. We evaluated the vasorelaxation effects of insulin and IGF-I on porcine coronary epicardial vessels in vitro and elucidated possible mechanisms. Porcine epicardial arteries were contracted with 10(-7) mol/L endothelin-1 and relaxed with cumulative concentrations of either insulin or IGF-I (10(-12) to 10(-7) mol/L). The above experiments were repeated in vessels without endothelium. Vessels were also incubated with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 10(-4) mol/L) with and without 10(-3.5) mol/L L-arginine, the potassium channel blocker tetraethylammonium (TEA; 10(-2) mol/L), and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-alpha]quinoxalin-1-one (ODQ; 10(-5.5) mol/L); vessels were then contracted with endothelin-1 and relaxed with insulin or IGF-I. Insulin and IGF-I were also added after contraction with 60 mmol/L KCl. Insulin and IGF-I caused a similar decrease in coronary epicardial tension after contraction with endothelin-1 (relaxation of 28+/-4% [n=7] and 25+/-3% [n=8] with insulin and IGF-I, respectively; P<0.0001 for both peptides). Removal of the endothelium did not affect these responses. Incubation with L-NMMA, but not ODQ, attenuated the vasorelaxation response to insulin and IGF in vessels without endothelium. L-Arginine did not reverse this effect of L-NMMA. KCl and TEA attenuated the vasorelaxation effect of both insulin and IGF-I. Thus, both insulin and IGF-I caused non-endothelium-dependent coronary vasorelaxation in vitro, probably through a mechanism involving the activation of potassium channels. These findings suggest that insulin and IGF-I participate in the regulation of coronary vasomotor tone.

Animals↗

PubMed1998

Profiles of the Endocrine Clinic: the Mayo Clinic.

It is evident that clinical endocrinology, as a discipline, is entering a particularly exciting period in its evolution. Knowledge gained from basic and clinical research is being translated at the bedside for the benefit of our patients. The emergence of new drugs and novel treatment strategies has equipped clinical endocrinologists with the tools to more successfully combat many old enemies, such as diabetes and osteoporosis. Realization of full benefit from these exciting new tools requires a practice model in which the clinical endocrinologist's role is preeminent and is coordinated and integrated with those of practitioners drawn from other disciplines. The Mayo Division of Endocrinology, Metabolism, and Nutrition provides one such model of highly integrated care. We believe that as the pace of knowledge regarding basic mechanisms of disease and their treatment quickens, such integrated divisions will prove well suited to deliver the highest quality care to people with endocrine disorders.

Academic Medical Centers↗

PubMed1998

Overnight normalization of glucose concentrations improves hepatic but not extrahepatic insulin action in subjects with type 2 diabetes mellitus.

Subjects with poorly controlled type 2 diabetes are both hyperglycemic and insulin resistant. To determine whether short term restoration of normoglycemia improves insulin action, hyperinsulinemic (approximately 300 pmol/L) euglycemic clamps were performed in diabetic subjects after either overnight infusion of saline or overnight infusion of insulin in amounts sufficient to maintain euglycemia throughout the night. Fasting glucose concentrations (5.2 +/- 0.2 vs. 11.9 +/- 1.4 mmol/L; P < 0.01) and rates of endogenous glucose production (13.0 +/- 1.1 vs. 18.6 +/- 1.6 mumol/kg.min; P < 0.05) were both lower after overnight insulin than overnight saline. Insulin-induced stimulation of glucose uptake (to 34.9 +/- 6.8 vs. 28.8 +/- 3.4 mumol/kg.min; P = 0.2) and inhibition of free fatty acids (to 0.13 +/- 0.03 vs. 0.12 +/- 0.04 mmol/L; P = 0.6) did not differ after overnight saline and overnight insulin. In contrast, endogenous glucose production during the final hour of the hyperinsulinemic clamps (i.e. when glucose concentrations were the same) remained higher (P = 0.05) after overnight saline than after overnight insulin (5.5 +/- 1.5 vs. 0.02 +/- 1.4 mumol/kg.min). Thus, acute restoration of euglycemia by means of an overnight insulin infusion improves hepatic (and perhaps renal) but not extrahepatic insulin action.

Blood Glucose↗

PubMed1998

Normal glucose-induced suppression of glucose production but impaired stimulation of glucose disposal in type 2 diabetes: evidence for a concentration-dependent defect in uptake.

The present studies were undertaken to determine whether people with type 2 diabetes are resistant to the effects of glucose as well as insulin. Diabetic and nondiabetic subjects were studied on three occasions. Hormone secretion was inhibited with somatostatin. Insulin concentrations were kept at "basal" levels (referred to as low insulin infusion) from 0 to 180 min then increased to approximately 200 pmol/l from 181 to 360 min (referred to as high insulin infusion). Glucose concentrations were clamped at either approximately 95, approximately 130, or approximately 165 mg/dl on each occasion. In the presence of basal insulin concentrations, a progressive increase in glucose from 95 to 130 to 165 mg/dl was accompanied by a comparable and progressive decrease (P = 0.001 to 0.003 by analysis of variance [ANOVA]) in endogenous glucose production (measured with [6-(3)H]glucose) and total glucose output (measured with [2-(3)H]glucose) and incorporation of 14CO2 into glucose (an index of gluconeogenesis) in both diabetic and nondiabetic subjects, indicating normal hepatic (and perhaps renal) response to glucose. In the nondiabetic subjects, an increase in glucose concentration from 95 to 130 to 165 mg/dl resulted in a progressive increase in glucose disappearance during both the low (19.9 +/- 1.8 to 23.6 +/- 1.8 to 25.4 +/- 1.6 micromol x kg(-1) x min(-1); P = 0.003 by ANOVA) and high (36.4 +/- 3.1 to 47.6 +/- 4.5 to 61.1 +/- 7.0 micromol x kg(-1) x min(-1); P = 0.001 by ANOVA) insulin infusions. In contrast, in the diabetic subjects, whereas an increase in glucose from 95 to 130 mg/dl resulted in an increase in glucose disappearance during both the low (P = 0.001) and high (P = 0.01) dose insulin infusions, a further increase in glucose concentration to 165 mg/dl had no further effect (P = 0.41 and 0.38) on disappearance at either insulin dose (low: 14.2 +/- 0.8 to 18.2 +/- 1.1 to 18.7 +/- 2.4 micromol x kg(-1) x min(-1); high: 21.0 +/- 3.2 to 33.9 +/- 6.4 to 32.5 +/- 8.0 micromol x kg(-1) x min(-1) for 95, 130, and 165 mg/dl, respectively). We conclude that whereas glucose-induced stimulation of its own uptake is abnormal in type 2 diabetes, glucose-induced suppression of endogenous glucose production and output is not. The abnormality in uptake occurs in the presence of both basal and high insulin concentrations and is evident at glucose concentrations above but not below 130 mg/dl, implying a defect in a glucose-responsive step.

Blood Glucose↗