Short time effects of growth hormone on glucose metabolism and insulin and glucagon secretion in normal man.

The present study was undertaken in order to evaluate the acute metabolic and hormonal effects of human growth hormone in healthy subjects. Glucose turnover, plasma glucose, FFA, insulin, C-peptide, glucagon, and somatostatin concentrations were determined in the fasting state after a bolus injection of placebo or growth hormone in quantities producing increases in plasma growth hormone levels within the normal physiological range. We found that growth hormone administration resulted in negligible changes in plasma glucose, no significant changes in appearance or disappearance rates of glucose, a moderate increase in FFA and a moderate fall in plasma insulin, C-peptide and glucagon concentrations, while plasma somatostatin levels were unchanged. These findings suggest that rapid changes in plasma growth hormone concentrations, corresponding to the fluctuations seen during normal daily life, may play a role in the short time regulation of blood glucose concentration through an inhibition of insulin and glucagon secretion.     

EFFECT OF EXOGENOUS INSULIN ON FASTING SERUM LEVELS OF GASTRIC INHIBITORY POLYPEPTIDE (GIP) IN JUVENILE DIABETES

The effect of insulin on fasting levels of immunoreactive gastric inhibitory polypeptide (IR-GIP) has been examined in insulin-dependent, juvenile-type diabetics who were well-controlled with two doses of an intermediate insulin. After withdrawal of the evening insulin injection the fasting blood glucose and serum IR-GIP levels were elevated and decreased significantly following intravenous insulin towards normal values. There was a significant positive correlation between levels of blood glucose and serum IR-GIP before and during insulin application. It is suggested that fasting serum GIP levels increase in case of insulin deficiency because basal GIP secretion is suppressed by normal insulin levels.     

Individualized low-dose growth hormone (GH) treatment in GH-deficient adults with childhood-onset disease: metabolic effects during fasting and hypoglycemia.

Growth hormone (GH) has insulin-antagonistic effects, and GH secretion is augmented during fasting and hypoglycemia. In the present study, 10 patients aged 21 to 28 years with childhood-onset GH deficiency (GHD) were studied during a 24-hour fast and a hypoglycemic glucose clamp before and after 9 months of GH replacement. During the 24-hour fast, blood glucose, serum insulin, and serum free fatty acid (FFA) levels were measured. In the hypoglycemic clamp, the counterregulatory hormones (plasma catecholamines, serum glucagon, and serum cortisol), serum insulin-like growth factor (IGF) binding protein-1 (IGFBP-1), serum FFA, and glucose uptake were measured. The GH dose was adjusted to the response of serum IGF-I, and the median GH dose was 0.14 IU/kg/wk (range, 0.08 to 0.19). At the end of the study, serum IGF-I levels were normalized in all but one patient, in whom serum IGF-I was above the normal range. Nine months of GH treatment did not cause any significant changes in the blood glucose level, insulin to glucose ratio, or serum FFA level during the 24-hour fast, and none of the patients experienced hypoglycemia either before or after GH treatment. However, GH therapy resulted in increased insulin resistance during hypoglycemia, without changes in the counterregulatory hormonal responses, serum IGFBP-1, or serum FFA.     

Glucose tolerance, serum insulin and lipid abnormalities in patients with coronary heart disease.

Blood glucose, free fatty acid and insulin responses to oral glucose and the fasting serum lipids were measured in 3 groups: 32 non-obese (mean age: 47.5 years) and 9 obese (mean age: 84.5 years), male patients with coronary heart disease and 12 non-obese male controls (mean age: 46.5 years). The oral glucose tolerance tests were repeated after 3 years in 16 of the non-obese patients with coronary heart disease. The results were as follows: 1) Glucose tolerance was impaired in 19 of 32 non-obese patients (59.4%). There was a significant correlation between impaired glucose tolerance and hyperlipidemia (hypercholesterolemia and/or hypertriglyceridemia). 2) In obese patients FFA levels at 30, 60, and 120 min after oral glucose administration were significantly elevated and FFA decrease was delayed with a drop to minimum levels at 180 min. 3) The insulin response after oral glucose administration in the group of non-obese patients with normal glucose tolerance was similar to that of non-obese controls. In the group of non-obese patients with impaired glucose tolerance, serum insulin levels went up to normal levels, but the peak was delayed. The serum insulin levels in obese patients were significantly higher than those of controls of 0, 60, 120, and 180 min. After 3 years the change in insulin response to oral glucose was not related to anginal symptoms or ECG findings, but was related to body weight change in patients with minor changes in glucose tolerance. 4) The metabolic pattern in the non-obese group with impaired glucose tolerance resembled that of "mild diabetes" in delayed response of insulin and FFA, and mild hyperlipidemia. These findings suggest that obesity may contribute to hyperinsulinemia in patients with coronary heart disease and that impaired glucose tolerance observed in patients with coronary heart disease is in part due to "latent diabetes".     

Studies on serum ketone bodies in patients with hyperthyroidism

In order to investigate effects of thyroid hormone on ketone bodies metabolism, fasting levels of serum ketone bodies, serum free fatty acids (FFA), serum insulin (IRI), plasma glucagon (IRG) and plasma glucose were examined in 29 untreated patients with hyperthyroidism and 20 healthy subjects. In 21 patients the levels of serum ketone bodies were re-examined when euthyroidism was achieved after treatment. In all of healthy subjects and 17 patients changes in the levels of serum ketone bodies after oral glucose load were examined. The results were as follows: 1). Fasting levels of serum FFA and total ketone bodies (TK), acetoacetate (AcAc), 3-hydroxy-beta-butylate (3OHBA), ratio of 3OHBA to AcAc in the patients were significantly higher than those in healthy subjects. The levels of IRI, IRG or ratio of IRG to IRI in the patients were not different from those in healthy subjects. In the patients, the fasting level of TK was significantly correlated with the level of FFA. 2). After oral glucose load the levels of TK and FFA in the patients decreased gradually. 3). The fasting levels of TK and FFA in the patients decreased when euthyroidism was achieved after treatment. It was suggested that the fasting levels of serum ketone bodies in patients with hyperthyroidism elevated probably due to activated lipolysis.     

A COMPARISON OF THE EFFECT OF LEVODOPA AND SOMATOSTATIN ON THE PLASMA LEVELS OF GROWTH HORMONE, INSULIN, GLUCAGON AND PROLACTIN IN ACROMEGALY

The acute suppressive effects of L-dopa and somatostatin (growth hormone release inhibiting hormone) on the elevated plasma GH concentrations of seven patients with acromegaly were compared. In addition the effects of the two agents on fasting concentrations of plasma glucose, insulin, glucagon and prolactin were studied. In six of the seven patients hourly samples for GH assay were taken from 08.00 to 20.00 hours on a control day. Synthetic cyclic somatostatin (100 mug) was infused intravenously in an albumin/saline solution over 75 min with a Harvard constant infusion pump. Levodopa 500 mg was given orally. Somatostatin infusion produced a reduction in plasma GH concentrations in six of seven patients (mean reduction 55%). L-Dopa produced a reduction in plasma GH concentrations in the same six patients (mean reduction 52%). The minimum GH concentrations achieved in the two tests were comparable and did not differ significantly from the minimum GH concentrations recorded during the 12 h control study. Mean plasma insulin and glucagon concentrations were also significantly reduced during the somatostatin infusion (P less than 0-025; P less than 0-05 respectively). Plasma glucose concentrations did not change. L-Dopa did not alter mean plasma glucose, insulin or glucagon values. Somatostatin did not alter prolactin values but L-Dopa suppressed basal values to less than 2 ng/ml in five patients. This study shows that the plasma GH change after the administration of L-dopa and somatostatin in acromegaly is comparable and confirms the pancreatic effects of somatostatin.     

CHANGES IN SERUM INSULIN CONCENTRATION DURING PUBERTY AND THEIR RELATIONSHIP TO GROWTH HORMONE

In 40 tall and short children we have demonstrated using oral glucose tolerance tests that there is an increase in serum insulin concentration during puberty with no change in blood glucose concentration. Fasting serum insulin concentration rose from a pre-pubertal value between 4.0 and 5.7 mU/l to values between 11.0 and 14.6 mU/l during puberty. This rise in both fasting serum insulin concentration and the incremental area under the insulin curve is probably due to changes in circulating GH concentrations. In 16 tall girls a rise in serum GH concentration was observed during pubertal growth and the rise was accompanied by a two- to three-fold increase in fasting serum insulin concentration. In 13 children in whom 24 h growth hormone profiles were recorded higher insulin concentrations were seen in those who secreted the most growth hormone. These data suggest that during pubertal growth in diabetic children the standard dosage of insulin administered (0.9 units/kg per day) should be doubled or possibly tripled to maintain good metabolic control and maximize pubertal growth.     

Studies in congenital generalized lipodystrophy. IV. Effect of muscular exercise on carbohydrate and fat metabolism including plasma levels of IRI and HGH.

Two patients with congenital generalized lipodystrophy have been studied at rest, and during and after long-term exercise at different carefully measured work loads. The two patients represented different stages of diabetes development. Both patients derived most of their energy used during muscular exercise from carbohydrate, and comparatively little from fat. FFA levels remained low throughout the period of observation in contrast to normal individuals and patients with juvinile diabetes. The data presented seem to show that deposition of glucose and free fatty acids (FFA) as triglyceride, must be impaired and are not compatible with the concept of increased triglyceride turnover in the adipocytes. The fall in blood glucose concentration (BCG) was less than in normal individuals and juvenile diabetes during exercise, and the glucose tolerance remained unchanged following work stop in both patients (k-values unchanged), in contrast to normal persons and patients with juvenile diabetes. Both patients showed significant falls in circulating immuno-reactive insulin (IRI) levels during exercise irrespective of a rise or fall in BGC. Thus, the exercise itself might activate endogenous mechanisms which could, on the one hand increase the circulating BGC, and at the same time force circulating IRI to decrease, thus disturbing the well-known relationship between circulating glucose and IRI levels as has been exhibited in normal subjects. The high IRI levels, also during exercise in these patients, indicate a relative insulin resistance in the muscles, but less marked than the insulin resistance in the adipose tissue. The IRI response after glucose infusion did not change significantly with increasing work loads with one exception. Exercose did not alter significantly the human growth hormone (HGH) levels in either the diabetic or the non-diabetic patient indicating an abnormal regulation of the HGH secretion in congenital lipodystrophy.     

PLASMA FREE FATTY ACID TURNOVER IN TOTAL LIPODYSTROPHY

Basal free fatty acid (FFA) turnover was found to be elevated or at the upper limit of normal in a patient with total lipodystrophy. The decrease in plasma FFA concentration which occurred after intravenous administration of insulin was shown to be primarily due to a fall in the inflow of FFA into the circulation. These results provide support for the suggestion that adipocytes in total lipodystrophy are able to synthesize triglyceride, but that they are unable to store it because of rapid lipolysis.     

Ambient plasma free fatty acid concentrations in noninsulin-dependent diabetes mellitus: evidence for insulin resistance

Plasma glucose, insulin, and FFA concentrations were determined in 15 normal subjects and 15 patients with noninsulin-dependent diabetes mellitus (NIDDM) from 0800 to 1600 h. Breakfast and lunch were consumed at 0800 and 1200 h, respectively, and plasma concentrations were measured at hourly intervals from 0800-1600 h. Plasma glucose concentrations between 0800 and 1600 h were significantly elevated in patients with NIDDM, and the higher the fasting glucose level, the greater the postprandial hyperglycemia. Hyperglycemia in patients with NIDDM was associated with plasma insulin levels that were significantly higher (P less than 0.001) than those in normal subjects, and substantial hyperinsulinemia occurred between 0800 and 1600 h in patients with mild NIDDM (fasting plasma glucose concentrations, less than 140 mg/dl). Both fasting and postprandial FFA levels were also increased in patients with NIDDM (P less than 0.001), and the greater the plasma glucose response, the higher the FFA response (r = 0.70; P less than 0.001). However, there was no significant correlation between plasma insulin and FFA concentrations. More specifically, hyperinsulinemic patients with mild diabetes (fasting plasma glucose, less than 140 mg/dl) maintained normal ambient FFA levels, while FFA concentrations were significantly elevated in patients with severe NIDDM (fasting plasma glucose, greater than 250 mg/dl), with insulin concentrations comparable to those in normal subjects. These results demonstrate that patients with NIDDM are not capable of maintaining normal plasma FFA concentrations. This defect in FFA metabolism is proportionate to the magnitude of hyperglycemia and occurs despite the presence of elevated levels of plasma insulin. These results are consistent with the view that insulin resistance in NIDDM also involves the ability of insulin to regulate FFA metabolism.     

THE EFFECT OF SULPIRIDE INDUCED HYPERPROLACTINAEMIA ON GLUCOSE TOLERANCE AND INSULIN SECRETION IN NORMAL SUBJECTS

Blood glucose concentration and insulin secretion expressed by peripheral plasma insulin (IRI) and C-peptide levels were measured during saline and sulpiride infusion in five normal men. In another experiment the same variables were analysed in six normal males before and during oral sulpiride treatment for 5 days. The i.v. and oral administration of sulpiride resulted in a significant rise in serum prolactin levels. The stimulated serum prolactin concentrations were equivalent to those seen during stress. The sulpiride induced hyperprolactinaemia did not change blood-glucose, plasma IRI levels, hepatic insulin removal and glucose utilization during basal conditions or after i.v. glucose administration.     

Somatotrophic diabetes: Insulin release responses to arginine and glucagon in dogs

Summary Growth hormone injected daily in 6 dogs for 6 days caused a 20-fold elevation in fasting serum immunoreactive insulin (IRI) without appreciable change in serum glucose in 1 day. In the somatotrophic diabetes that occurred after 2 days, the hyperinsulinaemia was maintained and the serum IRI/glucose (I/G) ratio declined from the early high level but remained elevated. During this treatment, in response to glucose infusion, the rise in serum IRI above the initially high fasting level was 16 times the normal. In response to glucagon, the rise in IRI was twice the normal and the rise in glucose was more prolonged, resulting in a decline in the I/G ratio. In response to arginine infusion, the rise in serum IRI was 8 times the normal and the rise in the I/G ratio was twice normal. Following a meal, the rise in serum IRI was 8 times the normal. Thus, with growth hormone treatment the insulin secretory responses to these stimulating factors were magnified over the already elevated fasting level of secretion. The insulin content of the pancreas was reduced to less than 10% of normal by growth hormone treatment for 6 days, due apparently to elevation of the rate of secretion over the rate of formation of insulin.     

The effect of glibenclamide administration on insulin sensitivity and insulin binding to monocytes in normal subjects

Insulin sensitivity and insulin binding to monocytes were determined in seven normal subjects before and after one week's treatment with glibenclamide 2 mg three times daily. Glibenclamide administration produced a 60% increase in maximal specific insulin binding to monocytes. There was no effect on the blood glucose response to an intravenous bolus of insulin but fasting blood glucose was significantly elevated following glibenclamide treatment. Statistically significant changes in the fasting levels of plasma C-peptide and serum proinsulin were not detected.     

家族性高血压病患者的胰岛素抗性及其受体变化

我们通过对15例家族性高血压病患者和10例年龄、性别、体重指数相当的正常对照者的比较发现,两者的空腹血糖和血清胰岛素水平相当,均正常;但家族性高血压病患者血糖和胰岛素的反应曲线下面积显著性高于正常对照组,且恢复时间显著延长。这证明:家族性高血压病患者存在糖耐量异常和胰岛素抗性,并且家族性高血压病患者的红细胞胰岛素受体数目减少。进一步分析发现,其特异性胰岛素结合率与基础的血糖和胰岛素水平,以及服糖180分钟内血糖反应曲线下面积无关,但与服糖后180分钟内胰岛素反应曲线下面积呈负相关。这提示,家族性高血压病患者红细胞胰岛素受体缺陷,可加重胰岛素抗性,但不是产生糖耐量减低和胰岛素抗性的主要原因。     

Propranolol and hyperthyroidism: serum free fatty acids and glucose-induced insulin release in nondiabetic thyrotoxic patients during treatment to clinical compensation

Glucose-induced insulin secretion was studied in 10 hyperthyroid patients, without personal or familial diabetic background, treated with increasing weekly doses of propranolol until clinical compensation was obtained. Intravenous glucose tolerance tests (25g) with concomitant determination of serum glucose, insulin and FFA were done before treatment, at 240 mg/day of propranolol and after clinical compensation. Patients were divided into two groups according to laboratory data and propranolol dosage needed for clinical compensation (group A: 240 mg/day; group B: 320-400 mg/day). Fasting serum insulin, glucose disappearance rate, and estimates of total insulin secretion after intravenous glucose did not change significantly during propranolol therapy and were within the normal range. Fasting FFA of untreated patients were significantly higher than control values (p less than 0.001), but a significant decrease was already seen at 240 mg/day of propranolol, even before clinical compensation. There was a marked difference in the insulin secretion pattern of thyrotoxic patients as compared to controls. Serum insulin and insulin:glucose ratios increased promptly, and at 5 min after glucose reached significantly higher levels than in normal subjects, before treatment as well as after clinical compensation with the propranolol therapy. Both the increased levels of FFA and of T3 could be involved in this pattern of the insulin response of nondiabetic thyrotoxic patients, since the secretion of insulin during the first 10 min after intravenous glucose was directly correlated to fasting serum FFA before propranolol, and serum T3 was directly correlated with total insulin response after clinical compensation. Furthermore the comparison of the results obtained in group A and group B patients raises the possibility that an increased beta-cell responsiveness to beta-adrenergic stimuli might also be involved in this pattern of insulin secretion.     

Interactions of insulin and epinephrine in human metabolism: their influence on carbohydrate and lipid oxidation rate.

Two groups of normal male subjects were given an infusion of insulin and an infusion of epinephrine + insulin respectively. Blood glucose, plasma free fatty acids (FFA), insulin, growth hormone, cortisol, and urinary catecholamines were determined. Continuous indirect calorimetry was used to measure metabolic rate and oxidation rates of carbohydrate and lipids. The first group (n equals 7) received a 30-minute insulin infusion (0.1 IU/kg). While blood glucose and plasma FFA decreased, carbohydrate oxidation and metabolic rate significantly increased after some delay, whereas lipid oxidation decreased. The increase in carbohydrate oxidation amounted to 5 g/120 min. The decrease in blood glucose during insulin administration did not correlate with the increase in carbohydrate oxidation. In the second group (n equals 7), a 150-minute epinephrine infusion (900 mug in 500 ml saline) was administered, and superimposed upon it, a similar insulin infusion initiated after 60 min. Epinephrine alone increased blood glucose and plasma FFA levels, and decreased insulinemia. The rise in the metabolic rate was sharp and significant. After a short but significant increase the oxidation rate of carbohydrate decreased, whereas that of lipids markedly rose. This increase significantly correlated with that in FFA. Addition of insulin markedly decreased the elevated FFA levels and lowered blood glucose. After some delay this was followed by a marked increase in carbohydrate oxidation and a decrease in lipid oxidation. In this test the total increase in carbohydrate oxidation was 11 g/120 min. In comparison with the insulin test, this double amount seems to correlate well with the higher blood glucose levels measured before insulin administration. The results suggest that insulin indirectly stimulates carbohydrate oxidation by facilitating glucose transport into the cells and lowering FFA levels, and that epinephrine favours lipid oxidation through its lipolytic effects and its suppression of insulin release.     

The effect of diet upon carbohydrate metabolism, insulin resistance, and blood pressure in congenital total lipoatrophic diabetes

An 11-yr-old female with congenital total lipodystrophy had nonketotic hyperglycemia with resistance to both endogenous and exogenous insulin and systemic hypertension. Twenty-four hour patterns of secretion and mean concentrations of growth hormone, cortisol, Luteinizing Hormone (LH), and Follicle-Stimulating Hormone (FSH) were normal. Plasma glucagon was elevated during periods of hyperglycemia, but was normal during normoglycemia, even though insulin resistance was still evident. Insulin receptor density and affinity for insulin as determined in monocytes and erythrocytes were normal during hyperglycemia. Therapy with insulin and pimozide were not effective in controlling hyperglycemia. However, a diet restricted to 1800–2000 cal per day of average sodium content resulted in euglycemia and normal blood pressure without insulin therapy. Fasting serum glucose decreased from 393 to 65 mg/dl. In addition, triglycerides decreased from 304 to 115 mg/dl, glucagon from 421 to 126 pg/ml, and liver size returned to normal. There was a correlation between blood pressure and fasting glucose: systolic, r = 0.725, n = 54, p < 0.001; diastolic, r = 0.424, n = 54, p < 0.001. Plasma renin activity (PRA) and plasma aldosterone (PA) levels were mildly elevated in both the hypertensive and normotensive states. Plasma renin activity was 2.15 ± 0.73, (SD) ng/ml/hr supine and 5.32 ± 1.81 upright over an 11-day period when urinary sodium excretion was 96.0 ± 25.5 meq/day. When fasting glucose levels were 332–393 mg/dl, glucose turnover was 1967 μmole/min (normal, 696 ± 120, SD), net glucose decay during i.v. glucose tolerance (IVGTT) 15.6 g/50 min/1.73m² (normal, 16.7 ± 3.7), and Kg was 0.52%/min (normal, 1.86 ± 0.51, SD). After intensive diet therapy, fasting glucose was 97 and glucose turnover was 810 μmole/min, net glucose decay was 15.18 and Kg was 0.92. When the subject was hyperglycemic, plasma alanine concentration was normal, as was alanine conversion to glucose. Basal unbound insulin levels were elevated during hyperglycemia and normal during euglycemia. Insulin release, which was negligible during the first IVGTT, had a more normal pattern during the second test. In this patient with lipoatrophy, insulin resistance did not appear to derive from known insulin antagonists. The data suggested that insulin resistance may derive from a reversible loss of coupling of a normal insulin receptor to metabolic pathways. This loss may be tissue specific, involving adipose tissue and liver but not muscle, and appears to occur at insulin levels that are increased but lower than would otherwise cause a loss of hormone responsiveness in normal and obese individuals. An unknown antagonist, if present, must be diet-dependent.     

HYPERINSULINAEMIA AND INSULIN RESISTANCE OF CIRRHOSIS: THE IMPORTANCE OF INSULIN HYPERSECRETION

The mechanism for the hyperinsulinaemia in cirrhosis was investigated using two different approaches. In the first study, the metabolic clearance rate of insulin was measured at steady state in 13 cirrhotic and 13 weight-matched control subjects. With comparable insulin infusion rates (1.00 +/- 0.19 versus 1.07 +/- 0.15 mU/kg/min), steady-state plasma insulin concentrations (104 +/- 25 versus 87 +/- 12 microU/ml; P greater than 0.5) and MCRIRI (13.6 +/- 1.6 versus 15.4 +/- 2.0 ml/kg/min; P greater than 0.5) were similar. In the second study, fasting and oral glucose stimulated C-peptide/insulin ratios were compared in 16 cirrhotic and 18 weight matched control subjects. Although fasting glucose levels were significantly higher in the cirrhotic groups, all values were in the normal range (5.5 +/- 0.3 versus 4.8 +/- 0.1 mmol/l, P less than 0.02). However, fasting insulin (0.171 +/- 0.02 versus 0.068 +/- 0.004 nmol/l) and C-peptide (1.02 +/- 0.13 versus 0.42 +/- 0.02 nmol/l) were strikingly higher (P less than 0.001) in cirrhotic subjects. On the other hand, fasting C-peptide/insulin ratios were not statistically different in the two groups (6.18 +/- 0.52 versus 6.77 +/- 0.46; P greater than 0.3). This suggests that beta cell hypersecretion was the principal cause of the fasting hyperinsulinaemia, rather than decreased insulin hepatic extraction. Following the glucose load in 13 of the control and seven of the cirrhotic group, the C-peptide/insulin ratio fell in both groups but was significantly lower in the cirrhotic compared to control subjects at 30, 60 and 120 min, consistent with possible impairment of hepatic insulin extraction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Higher fasting plasma free Fatty Acid levels are associated with lower insulin secretion in children and adults and a higher incidence of type 2 diabetes

Context: There are limited data in humans on the association between fasting free fatty acid (FFA) levels and pancreatic β-cell function. Objective: Our objective was to examine this association in children and adults with normal glucose tolerance and to explore fasting FFA levels in relation to subsequent risk of impaired glucose tolerance (IGT) and type 2 diabetes (T2D). Design: We measured FFA, glucose, and insulin levels after an overnight fast and 30 min after an oral glucose load in 797 children aged 8 yr in the Avon Longitudinal Study of Parents and Children and 770 adults aged 44-71 yr in the Medical Research Council Ely Study. We calculated the homeostasis model assessment to estimate fasting insulin sensitivity, the insulinogenic index to estimate insulin secretion, and the disposition index to assess insulin secretion corrected for insulin sensitivity. Results: Higher fasting FFA levels were associated with lower insulin secretion in children (boys, P = 0.03; girls, P = 0.001) and adults (men, P = 0.03, women, P = 0.04). Associations with insulin sensitivity were more variable, but after adjustment for insulin sensitivity, higher fasting FFA levels remained associated with lower insulin secretion (disposition index). Compared with adults in the lowest tertile of fasting FFA levels, those in the middle and highest tertiles had a 3-fold higher incidence of IGT or T2D over the following 5-8 yr. Conclusions: Higher fasting FFA levels were consistently associated with lower insulin secretion in children and adults with normal glucose tolerance. Furthermore, higher fasting FFA levels were prospectively associated with a greater risk of subsequent IGT and T2D.     

Hypokalemic periodic paralysis associated with hypophosphatemia in a patient with hyperinsulinemia.

A 34-year-old man was admitted to the hospital because of acute quadriplegia. On admission, serum potassium was 2.1 mEq/L and serum inorganic phosphate was 1.4 mg/dL. Thyroid function was normal. Serum levels of aldosterone, cortisol, and intact parathyroid hormone were normal. Fasting plasma glucose was 109 mg/dL, and fasting serum insulin was 25.0 U/mL. Shortly after intravenous supplementation of potassium, muscle strength was normalized. Oral glucose tolerance test revealed impaired glucose tolerance and hyperresponse of insulin. During the oral glucose tolerance test, serum potassium and phosphate decreased significantly. These findings suggest that hyperinsulinemia and insulin-induced transmembrane shift of extracellular potassium and phosphate may have been involved in the abnormalities of serum electrolytes and development of hypokalemic periodic paralysis in the present patient.