Assessment of insulin action and glucose effectiveness in diabetic and nondiabetic humans.

Insulin concentrations in humans continuously change and typically increase only when glucose also increases such as with eating. In this setting, it is not known whether the severity of hepatic and extrahepatic insulin resistance is comparable and whether the ability of glucose to regulate its own uptake and release is defective in non-insulin-dependent diabetes mellitus (NIDDM). To address this question, NIDDM and nondiabetic subjects were studied when glucose concentrations were clamped at either 5 mM (euglycemia) or varied so as to mimic the glucose concentrations observed in nondiabetic humans after food ingestion (hyperglycemia). Insulin was infused so as to simulate a "nondiabetic" postprandial profile. During euglycemia, insulin increased glucose disposal in nondiabetic but not diabetic subjects indicating marked extrahepatic resistance. In contrast, insulin-induced suppression of glucose release was only minimally less (P < 0.05) in diabetic than nondiabetic subjects (-1.06 +/- 0.09 vs. -1.47 +/- 0.21 nmol.kg-1 per 4 h). Hyperglycemia substantially enhanced disposal in both groups. Glucose effectiveness measured as the magnitude of enhancement of disposal (0.59 +/- 0.18 vs. 0.62 +/- 0.17 nmollkg-1 per 4 h) and suppression of release (-0.36 +/- 0.12 vs. -0.14 +/- 0.12 nmol.kg-1 per 4 h) did not differ in the diabetic and nondiabetic subjects. In conclusion, when assessed in the presence of a physiological insulin profile, people with NIDDM demonstrate: (a) profound extrahepatic insulin resistance, (b) modest hepatic insulin resistance, and (c) normal ability of glucose to stimulate its own uptake and suppress its own release.

Microalbuminuria in patients with NIDDM: an overview.

We have come a long way in our understanding of the epidemiology, pathophysiology, and clinical significance of albuminuria in patients with NIDDM. However, substantial gaps remain to be defined. NIDDM nephropathy is a serious and increasingly burdensome disease for both the diabetic individual and the society at large. Onset of microalbuminuria, an early but common manifestation of NIDDM nephropathy, marks an ominous turn for the NIDDM patient, in whom its development forecasts a grave cardiovascular outcome. Interception of albuminuria with antihypertensive agents such as ACE inhibitors in otherwise healthy NIDDM subjects holds a significant promise but must first await further investigation.

The role of growth hormone in the development of diabetic retinopathy.

OBJECTIVE: To determine the role of growth hormone (GH) in the development of diabetic retinopathy. RESEARCH DESIGN AND METHODS: Medical records of 1,423 patients who had undergone insulin tolerance tests (1976-1991) at the Mayo Clinic were examined, and diabetic subjects were identified as either GH-deficient (GH increment after hypoglycemia < 5 micrograms/L and peak < 10 micrograms/L) or GH-sufficient. Prevalence of retinopathy was determined in these cases and in a cohort group of diabetic subjects selected to match the GH-deficient cases. These control patients (32 cases) were selected from medical records of individuals who had received medical care at Mayo during the same interval but who had not undergone insulin tolerance testing. RESULTS: Twenty-four patients with diabetes were identified, of whom 16 were GH-deficient and 8 GH-sufficient. Despite comparable age, duration of diabetes, and metabolic control, the prevalence of diabetic retinopathy in the GH-deficient group (2 of 16; 12.5%) was less (P < 0.05) than that observed in the GH-sufficient group (5 of 8; 62.5%). Prevalence in the GH-deficient group also was lower than that observed in the cohort control group (15 of 32, 47%). CONCLUSIONS: These data strongly suggest that GH contributes to the development of diabetic retinopathy in humans.

Effects of insulin on plasma magnesium in noninsulin-dependent diabetes mellitus: evidence for insulin resistance.

Insulin influences both glucose metabolism and magnesium homeostasis in humans. The present studies sought to determine whether insulin-induced stimulation of magnesium uptake is impaired in noninsulin-dependent diabetes mellitus (NIDDM) and enhanced by acute hyperglycemia. To do so, we measured plasma magnesium concentrations in diabetic and nondiabetic subjects on two occasions: once when glucose concentrations were maintained constant and once when glucose concentrations were varied to mimic a postprandial pattern. The same amount of insulin was infused on both occasions in a manner that reproduced the systemic insulin concentrations normally observed after glucose ingestion. During the prandial insulin infusion, the decrement in the plasma magnesium concentration was lower (P < 0.05) in the diabetic patients than that in the nondiabetic subjects during both the euglycemic (4.1 +/- 0.9 vs. 7.8 +/- 1.3 mmol/L.4 h) and hyperglycemic (1.7 +/- 1.1 vs. 6.6 +/- 1.4 mmol/L.4 h) studies. Glucose disappearance also was lower (P < 0.05) in the diabetic patients than that in the nondiabetic subjects, and the insulin-induced decrement in plasma magnesium was correlated (P < 0.01) with glucose disappearance. On the other hand, despite higher (P < 0.05) rates of disappearance in the hyperglycemic than euglycemic experiments, the decrement in plasma magnesium did not differ in either group on either occasion. We conclude that insulin resistance in subjects with NIDDM impairs the ability of insulin to stimulate magnesium as well as glucose uptake.

Prevalence of microalbuminuria in Saudi Arabians with non-insulin-dependent diabetes mellitus: a clinic-based study.

Prevalence of diabetic nephropathy varies in different racial groups, being especially high in communities that have abandoned an active traditional living and embraced a modern but sedentary life-style. As a new and rapidly developing country, Saudi Arabia has witnessed impressive changes in socio-economic growth and development and concurrently, a disturbing trend in non-insulin-dependent diabetes mellitus (NIDDM). These observations therefore prompted us to investigate the prevalence of microalbuminuria among Saudi Arabians with NIDDM. Two hundred and eleven patients attending a large Diabetic Clinic in Riyadh were screened for microalbuminuria (30-300 mg/24 h). Twenty-seven subjects had clinical proteinuria (dipstick-positive) and were excluded, leaving 184 cases for analysis. Seventy-six subjects (76/184, 41.3%) had microalbuminuria. These subjects had higher fasting plasma glucose concentrations (P = 0.002) and greater body mass index (P = 0.049) than subjects with normal albumin excretion rate (< 30 mg/24 h). There were no significant differences between subjects with and without microalbuminuria with regards to fasting total plasma cholesterol and triglycerides concentrations, frequency of hypertension, duration of diabetes or type of therapy for diabetes. In multivariate analysis, glycaemia (P < 0.005) and years since diagnosis of diabetes (P = 0.05) remained independently associated with albumin excretion rate. We conclude that microalbuminuria is exceedingly common in a clinic-based population of Saudi Arabians with NIDDM and its presence is closely related to glycaemic control. Whether the prevalence of microalbuminuria is truly increased in the diabetic population at large in Saudi Arabia must now await further population-based studies.

Diabetes care in the wake of the United Kingdom Prospective Diabetes Study.

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The diagnosis of diabetes mellitus. A contest between 3 points!

A major debate is currently taking place on the world diabetes scene on the merits of fasting versus 2-hour postprandial glucose concentrations as a reference point for the diagnosis of diabetes. Other time points of the oral glucose tolerance test on the other hand, seem to attract little attention. In Saudi Arabia however, we have been intrigued by the scale and severity of hyperglycemia observed at one-hour following glucose load. Plasma glucose concentration one-hour postprandially is strikingly abnormal amongst native Saudis and interestingly, is associated with insulin resistance and features of syndrome X. Such observations have prompted us to call into question the wisdom of current practices, namely of excluding the one-hour plasma glucose concentration in the diagnosis of diabetes. In the proceeding article therefore, we describe in detail our local observations and debate the wider scientific and historical issues surrounding the place of one-hour glucose concentration as a potentially useful diagnostic point in the detection and classification of glucose intolerance.

Obesity and overweight in type II diabetes mellitus patients in Saudi Arabia.

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Treatment of cancer associated hypercalcaemia with combined aminohydroxypropylidene diphosphonate and calcitonin.

Eight patients with cancer associated hypercalcaemia were treated with the combination of aminohydroxypropylidene diphosphonate and salmon calcitonin for six days. Serum calcium concentration fell significantly within 24 hours of starting treatment due to a reduction in bone resorption and renal tubular calcium reabsorption. In the longer term hypercalcaemia was controlled by a further progressive reduction in bone resorption, which persisted for six days after treatment was stopped. Renal tubular calcium reabsorption, however, remained suppressed only during drug treatment. The rapid fall in serum calcium was attributable to the acute renal and skeletal effects of calcitonin, whereas in the longer term control of hypercalcaemia was due to diphosphonate mediated suppression of bone resorption. In view of the rapid effect and lack of toxicity, combined treatment with aminohydroxypropylidene diphosphonate and calcitonin would be of particular value in patients with severe hypercalcaemia in whom a quick but sustained reduction in the serum calcium concentration is desired.

Clinical experience with aminohydroxypropylidene bisphosphonate (APD) in the management of cancer-associated hypercalcaemia.

Fifty-five patients with symptoms caused by hypercalcaemia associated with cancer were treated with varying regimens of intravenously-administered aminohydroxypropylidene bisphosphonate after initial rehydration. Of 48 patients where adequate data were available, 32 (66 per cent) were rendered normocalcaemic and 16 (33 per cent) remained mildly hypercalcaemic. In these cases, failure to restore normocalcaemia was attributable to elevated renal tubular reabsorption of calcium in nine (18 per cent) and to inadequate suppression of bone resorption in seven (14 per cent). There was no significant difference in response and duration of effect (median 20 days) between single doses of 15, 25 and 45 mg, or when the 45 mg dose was administered over three, six or 24 h. These single dose regimens were similar in terms of effect on calcium levels and duration of action, to multiple daily doses of 15 mg for a mean of six days. While the effect of 5 mg dose was not significantly different from the higher doses, suppression of serum calcium levels was less marked and the effect on duration of action significantly shorter than with the 45 mg dose. In seven cases, treatment with a second course was less effective even with higher doses because suppression of bone resorption was poorer. These data indicate that there is little difference between the therapeutic effects of multiple 15 mg and single 15-45 mg intravenous infusions of aminohydroxypropylidene bisphosphonate in hypercalcaemia associated with cancer. A single intravenous infusion of a moderate dose (for example 15-30 mg) would be a convenient and effective way of treating most patients.

Treatment of hypercalcaemia in thyrotoxicosis with aminohydroxypropylidene diphosphonate.

Two patients had symptomatic hypercalcaemia accompanying thyrotoxicosis, despite initial treatment with volume repletion, beta blockade and antithyroid drugs. They were further managed with intravenous infusions of aminohydroxypropylidene diphosphonate resulting in rapid normalization of the serum calcium, with relief of symptoms. Aminohydroxypropylidene diphosphonate effectively suppressed the increased bone resorption of thyrotoxicosis without any undesirable adverse effects.