Effect of long term vitamin D supplementation on biomarkers of inflammation in Latino and African-American subjects with pre-diabetes and hypovitaminosis D.

Low vitamin D levels are associated with minority subjects, the metabolic syndrome, and inflammation. The effect of vitamin D supplementation on markers of inflammation has not been well studied. The aim of the study was to evaluate the effects of high doses of vitamin D supplementation for 1 year on serum biomarkers of inflammation in Latino and African-American subjects with pre-diabetes and hypovitaminosis D. Latino (n=69) and African-American (n=11) subjects who had both pre-diabetes and hypovitaminosis D with a mean age of 52.0 years, a BMI of 32.7 kg/m(2), and 70% of whom were females, were randomized to receive weekly doses (mean±SD) of vitamin D (85 300 IU±16 000) or placebo oil for 1 year. Serum levels of interleukin-6, tumor necrosis factor, highly sensitive C-reactive protein), plasminogen activator inhibitor 1, and insulin-like growth factor-1 were measured at baseline, 6, and 12 months. Serum 25-OH vitamin D levels of 22 ng/ml at baseline quickly rose to nearly 70 ng/ml in subjects receiving vitamin D and did not change in the placebo group. Two-way repeated measures ANOVA showed no differences between the 2 groups in any of the 5 selected parameters. High dose vitamin D supplementation for 1 year in minority subjects with pre-diabetes and hypovitaminosis D failed to affect serum biomarkers of inflammation.Clinical trial reg. no.: NCT00876928, clinicaltrials.gov.

Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes.

The consensus algorithm for the medical management of type 2 diabetes was published in August 2006 with the expectation that it would be updated, based on the availability of new interventions and new evidence to establish their clinical role. The authors continue to endorse the principles used to develop the algorithm and its major features. We are sensitive to the risks of changing the algorithm cavalierly or too frequently, without compelling new information. An update to the consensus algorithm published in January 2008 specifically addressed safety issues surrounding the thiazolidinediones. In this revision, we focus on the new classes of medications that now have more clinical data and experience.

The relationship of glycaemic control and triglycerides in patients with diabetes mellitus: a PreCIS Database Study.

AIMS: A common therapeutic approach in patients with type 2 diabetes mellitus who have elevated triglycerides (TGs) is to treat the hyperglycaemia before specifically targeting high TG. The aims of the current study were (i) to determine whether there was a relationship between glycated haemoglobin (HgbA1c) and TG levels at the baseline visit and (ii) to analyse the relationship between DeltaHgbA1c and DeltaTG after treatment. METHODS: Among 650 consecutive diabetic patients seen in the Cleveland Clinic Preventive Cardiology Department, 372 had both baseline and post-treatment HgbA1c and TG values. We analysed the relationship between baseline HgbA1c and TG as well as between the change in HgbA1c and the change in TG. For analysis, patients were divided into nine groups by tertiles of HgbA1c (< or =6.6, 6.7-7.8 and >7.8%) and TG (< or =1.75, 1.76-3.89 and >3.89 mmol/l) at baseline. RESULTS: At baseline, there was a small correlation between HgbA1c and TG (r(2) = 0.051; p < 0.001). For the entire group, there was a significant correlation between DeltaHgbA1c and DeltaTG from baseline to follow-up (r(2) = 0.077; p < 0.001). Analyses by tertiles showed that DeltaTG were only associated with changes in two groups: HgbA1c tertile 3 (>7.8%) and TG tertiles 2 (r(2) = 0.24; p < 0.0001) and 3 (r(2) = 0.187; p = 0.003). For every 1% change in the top tertile HgbA1c, there was a 9.3% change in TG (tertile 2) and a 9.8% change in TG (tertile 3). CONCLUSIONS: These observations suggest that for patients with diabetes mellitus and elevated TG, the effect of HgbA1c reduction has limited effects on TG reduction. Patients may benefit from TG-specific therapy initiated earlier rather than waiting to see effects of glycaemic control.

Increased insulin binding by hepatic plasma membranes from diabetic rats: normalization by insulin therapy.

Hepatic plasma membranes prepared from rats rendered diabetic by streptozotocin bound approximately twice as much insulin per 50 mug protein as control membranes. Glucagon binding of diabetic and control membranes was virtually identical. This increased insulin binding was not due to a nonspecific effect of streptozotocin, decreased degradation of insulin slower dissociation from its receptor, or a selective higher yield of membranes prepared from the diabetic livers. Diabetic and control membranes both showed negative cooperativity. Scatchard analysis suggested that the difference in binding was due to an enhanced binding capacity of the diabetic membranes rather than increased affinity of the binding sites. Increased insulin binding of diabetic membranes was returned to normal by insulin treatment. These data are consistent with the postulate that there is an inverse relationship between circulating insulin levels and insulin binding and that insulin may modulate its own receptor. However, since it has been reported that fat, muscle, and hepatic tissue from rats made diabetic by alloxan administration are insensitive to insulin, the capacity for binding can not be the sole factor determining the response to insulin in diabetes mellitus. Therefore, sensitivity of the diabetic liver to insulin is determined, at least in part, by events subsequent to the binding of insulin to its receptor.

Somatostatin blockade of acute and chronic stimuli of the endocrine pancreas and the consequences of this blockade on glucose homeostasis.

The nature and extent of somatostatin-induced inhibition of pancreatic endocrine secretion were studied by administration of a number of stimuli of either glucagon or insulin to over night fasted baboons with and without an infusion of linear somatostatin. The stimuli for acute-phase insulin release were intravenous pulses of glucose, tolbutamide, isoproterenol, and secretin. When given 15 min after the start of a somatostatin infusion, these agents were essentially unable to stimulate insulin secretion. Chronic insulin secretion was stimulated by infusions of either glucose or glucagon. Within 10 min of the start of a super-imposed infusion of somatostatin, insulin levels fell to less than 40 percent of prestimulus control and remained suppressed for the duration of the somatostatin infusion. Stimulation of glucagon secretion by insulin-induced hypoglycemia was also blocked by somatostatin. Plasma glucose decreased during somatostatin infusions except when superimposed upon an infusion of glucagon. Somatostatin had no effect on glucose production in a rat liver slice preparation. We conclude: (a) Somatostatin is a potent and so far universally effective inhibitor of both acute and chronic phases of stimulated insulin and glucagon secretion (b) The inhibitory effect is quickly reversible and the pattern of recovery of secretion is appropriate to prevailing signals; (c) Present evidence suggests that the effect of somatostatin on blood glucose is mediated through its effect on blood glucagon; (d) In the overnight-fasted baboon both in the basal state and 45 min into a 4-mg/kg-min glucose infusion, a somatostatin-induced fall in serum insulin levels appears to be unable to prevent a decrease in hepatic glucose production.

Alanine metabolism in skeletal muscle in tissue culture.

Alanine production by skeletal muscle in tissue culture was studied using an established myogenic line (L6) of rat skeletal muscle cells. Correlation analyses were performed on rates of metabolism of alanine, glucose, lactate and pyruvate over incubation periods up to 96 h. Alanine production did not correlate significantly with glucose utilization (r = 0.24, P less than 0.20). Alanine production, however, did correlate with lactate production (r = 0.72, P less than 0.0005) as well as medium (r = 0.50, P less than 0.025) and intracellular (r = 0.85, P less than 0.0005) pyruvate concentrations. The intercepts of the latter two correlation analyses indicated that when medium or cell pyruvate fell below 0.28 mM or 1 nmol/mg protein, respectively, net alanine consumption occurred. Alanine synthesis also correlated (r = 0.71, P less than 0.0005) with the percent change in the cell mass action ratio for the sum of the alanine and aspartate aminotransferase reactions, i.e., [alanine] [malate]/[aspartate] [lactate]. These results suggest that alanine production is not necessarily linked to the rate of glucose utilization but rater to pyruvate overflow above a critical intracellular level; under conditions of pyruvate overflow, alanine synthesis is driven by the tendency to establish equilibrium between metabolites of the linked amino acid transaminases in skeletal muscle.

The hexosamine biosynthetic pathway and glucose-induced down regulation of glucose transport in L6 myotubes.

Based on experiments in cultured adipocytes, it has been proposed that glucose-induced down regulation of glucose transport is mediated by the conversion of fructose-6-phosphate to glucosamine-6-phosphate via the first and rate-determining enzyme of the hexosamine biosynthetic pathway, glutamine: fructose-6-phosphate amidotransferase (glutamine hexosephosphate aminotransferase). Evidence for this assertion was: (a) L-glutamine, the provider group for the aminotransferase was essential; (b) two inhibitors of glutamine hexosephosphate aminotransferase, 6-diazo-5-oxonorleucine (L form) and azaserine, blocked glucose-induced down regulation of glucose transport; (c) azaserine inhibited the activity of the aminotransferase, (d) glucosamine, which enters the hexosamine pathway distal to this enzyme was 40-times more potent than glucose; and (e) azaserine was unable to block the effect of glucosamine. Since muscle is quantitatively much more important than adipose tissue for whole body glucose utilization, we sought to determine if the hexosamine pathway was involved in glucose-induced down regulation of glucose transport in L6 myotubes. Glucose was effective, both in the presence and absence of glutamine in the incubation media. Glucosamine was also effective but was as equipotent as glucose. Small amounts of glutamine hexosephosphate aminotransferase were present in the L6 myotubes and although the leucine derivative (20 microM) inhibited the enzyme, it did not impair glucose-induced down regulation of glucose transport. Total GLUT-1 levels were similar when the cells were incubated in the absence or presence of 5 mM glucose or glucosamine although glucosamine was associated with a marked increase in a lower molecular weight band. These results do not suggest that the hexosamine biosynthetic pathway is involved in glucose-induced down regulation of glucose transport in L6 myotubes. Thus, this phenomenon is regulated differently in muscle and fat.

Metabolic studies in the pyelonephritic rat.

Insulin antagonism characterizes infection, but the mechanism is unknown. Previous studies have been performed during the acute catabolic stage of infection, and the resultant metabolic changes reflect this decreased food intake and weight loss. To delineate metabolic alterations due to infection itself, rats with pyelonephritis induced by tail-vein injection of 1 ml. of Streptococcus faecalis (10(9) bacteria per milliliter) were studied two weeks later during a period of near-normal weight gain and food intake. Fasting growth hormone concentrations (nanograms per milliliter) in the pyelonephritic rats were nearly five times normal (45.8 vs. 9.9). Intra-arterial glucose and insulin tolerance tests were impaired. Early glucose-induced insulin release was depressed. Fat pads from infected rats manifested higher basal lipolysis per cell. Glycerol-mediated gluconeogenesis by liver slices was decreased. This pathway was unaffected by insulin in infected rats but readily inhibited in control rats. The following metabolic parameters were similar in control and infected animals: (in vivo) fasting concentrations of plasma glucose, free fatty acids, triglycerides, total corticoids, creatinine, insulin, glucagon, molar ratios of insulin and glucagon, glucose and insulin responses to tolbutamide, and glucagon and free fatty acid suppression after glucose; (in vitro) glucose metabolism by muscle and fat, epinephrine- and theophylline-stimulated lipolysis and re-esterification by epididymal fat pads, fasting hepatic glycogen content, glucose production by liver slices with and without alanine. No plasma insulin antagonist was found in the infected rats. Metabolic alterations in infected rats can be demonstrated independently of the associated catabolism. Increased growth hormone secretion cannot explain all of these changes.

Insulin sensitivity of the large human adipocyte in vitro.

Adipose tissue from twelve normal-weight and ten obese subjects on weight-maintaining diets and nine obese subjects on hypocaloric diets was removed at surgery and incubated in vitro. Basal glucose oxidation correlated significantly (r = 0.68, p less than 0.005) with fat-cell diameter in subjects on weight-maintaining diets. This relationship was significantly altered (p less than 0.02) in subjects on calorie-restricted diets. In tissue from subjects on weight-maintaining diets, physiologic concentrations of insulin (25 muU./ml.) significantly increased glucose incorporation into carbon dioxide (p less than 0.005) and glycogen (p less than 0.001). Maximum insulin-stimulated glucose oxidation (increase over basal) was significantly enhanced (p less than 0.05) in tissue from obese subjects, whereas insulin-mediated glucose incorporation into glycogen was similar in controls and obese subjects on weight-maintaining diets. Insulin-stimulated glucose oxidation was imparied in tissue from subjects on hypocaloric diets although fat-cell diameter was similar to those of obese subjects on weight-maintaining diets. The effect of insulin on glucose incorporation into glycogen in isolated adipocytes was also studied. There was no correlation between insulin-stimulated glycogen synthesis and cell diameter. When cells from the same individual were separated into small and large adipocytes by differential flotation, the insulin effect was similar whether expressed as absolute or per cent increase over basal. These results indicate that in vitro glucose oxidation by adipose tissue, in both the absence and the presence of insulin, is largely determined by dietary factors. This may also be true for insulin-stimulated glycogen synthesis. No evidence is provided for the concept that the enlarged human fat cell of obesity is insensitive to insulin in vitro.

Antidiabetic action of vanadyl in rats independent of in vivo insulin-receptor kinase activity.

The effects of oral vanadyl sulfate administration for 9-12 days on carbohydrate and lipid metabolism in the basal state and on glucose dynamics during submaximal hyperinsulinemic clamps were investigated in nondiabetic and streptozocin-induced diabetic rats. Decreases in growth rate and water and food consumption were the only significant alterations noted in control animals receiving vanadyl. Administration of vanadyl to diabetic rats resulted in weight loss; a significant decrease in plasma glucose, triglyceride, and cholesterol levels; and decreases in food and water intake, without a concomitant change in plasma insulin concentrations. Vanadyl treatment did not modify either peripheral glucose utilization or hepatic glucose production in control rats during submaximal insulin clamps. In contrast, vanadyl therapy increased insulin-induced glucose utilization significantly and had a small but nonsignificant effect on insulin-mediated suppression of glucose production in diabetic rats. The tyrosine kinase activity of liver- and muscle-derived insulin receptors from diabetic rats that underwent clamp study, which reflected the in vivo phosphorylation state of insulin receptor, was not altered by vanadyl treatment. In conclusion, these results show that augmentation of peripheral glucose utilization is the major determinant of the antidiabetic action of vanadyl and support the notion that the action of vanadyl is independent of insulin-receptor kinase activity.

Glucose transport is rate limiting for skeletal muscle glucose metabolism in normal and STZ-induced diabetic rats.

To test the hypothesis that glucose transport is rate limiting for skeletal muscle glucose metabolism, intracellular free glucose was measured in in situ abdominal wall muscle and liver that were rapidly freeze-clamped and removed from normal and streptozocin-induced diabetic (STZ-D) Sprague-Dawley rats exposed to different concentrations of serum insulin and glucose achieved by 90-min glucose clamps. Three groups of anesthetized normal (n = 17) and three groups of STZ-D (n = 19) animals were studied. In each group, infusions were adjusted to expose rats to basal, euglycemic-hyperinsulinemic, and hyperglycemic-hyperinsulinemic conditions. Final steady-state serum glucose and insulin concentrations (mean +/- SE) achieved in the six groups ranged from 112 +/- 2 to 467 +/- 26 mg/dl and from 5.8 +/- 1.9 to 3644 +/- 116 microU/ml, respectively. Intracellular free-glucose content of all tissue was calculated from total tissue glucose content minus the contribution of glucose in extracellular water estimated with [14C]inulin. Intracellular free glucose was not detected in muscle of any of the experimental groups. However, intracellular free glucose was detected in liver from all normal and STZ-D rats, and the calculated intracellular concentrations of free glucose correlated with serum glucose concentrations (r = .68, P less than .001). We conclude that intracellular free glucose does not accumulate, regardless of glucose or insulin concentration, in normal skeletal muscle and muscle made insulin resistant (by STZ-D), suggesting that glucose transport remains rate limiting.

Glyburide-stimulated glucose transport in cultured muscle cells via protein kinase C-mediated pathway requiring new protein synthesis.

To study the mechanism of action of sulfonylurea agents on peripheral tissues without the potentially confounding influences of insulin, the direct effect of glyburide (i.e., in the absence of insulin) was evaluated in the L6 cultured myogenic cell line. Glyburide approximately doubled the incorporation of [14C]-glucose into glycogen. The rate-determining enzymes of glycogen metabolism, glycogen synthase and glycogen phosphorylase, were unaffected by the drug. Glucose transport (2-deoxyglucose uptake) was also approximately doubled. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) also doubled glucose transport and showed the same lag period (4-6 h) as glyburide before an effect occurred. Blockade of protein kinase C activity by either 1-(5-isoquinolinesulfonyl)-2 methyl piperazine (H7) or chronic exposure to TPA completely abolished the stimulation by glyburide. Cycloheximide, a protein synthesis inhibitor, also completely eliminated the effect of glyburide. The presence of ATP-sensitive K+ channels was assessed by measuring 86Rb efflux in ATP-depleted L6 muscle cells and RINm5F cells (which served as a positive control). Such channels were present and responded appropriately to glyburide and diazoxide in pancreatic beta-cells but were not present in muscle cells. Glyburide stimulation of glucose transport was completely eliminated by both Quin 2, an intracellular chelator of Ca2+, and verapamil, a Ca2+ channel blocker. However, glyburide did not raise intracellular Ca2+ levels. We conclude that glyburide stimulates glucose transport in cultured L6 muscle cells by a protein kinase C-mediated pathway that requires new protein synthesis. Although intracellular Ca2+ metabolism may also be involved, the initial step in the mechanism of action is probably different between pancreatic beta-cells and muscle cells.

Cardiomyocyte dysfunction in sucrose-fed rats is associated with insulin resistance.

Diabetes is associated with impaired cardiac dysfunction in both humans and animals. Specific phenotypic changes-prolonged action potentials, slowed cytosolic Ca2+ clearing, and slowed relaxation-that contribute to this whole heart dysfunction occur in isolated ventricular myocytes. The present study was designed to determine whether cardiomyocyte abnormalities occur early in the development of type 2 diabetes (in this case, insulin resistance) and whether an insulin-sensitizing drug (metformin) is cardioprotective. In the study, high-sucrose feeding was used to induce whole-body insulin resistance. Wistar rats were maintained for 7-10 weeks on a starch (ST) diet, sucrose (SU) diet, or diet supplemented with metformin (SU + MET). Whole-body insulin resistance was measured in SU and SU + MET rats by performing euglycemic-hyperinsulinemic clamps. Mechanical properties of isolated ventricular myocytes were measured by high-speed video edge detection, and [Ca2+]i transients were evaluated with Fura-2 AM. Untreated SU rats were insulin-resistant (glucose infusion rate [GIR] = 14.5 +/- 1.1 mg.kg(-1).min(-1)); metformin treatment in SU + MET rats prevented this metabolic abnormality (GIR = 20.0 +/- 2.2 mg.kg(-1).min(-1)). Indexes of myocyte shortening and relengthening were significantly longer in SU rats (area under the relaxation phase [AR/peak] = 103 +/- 3 msec) when compared to ST and SU + MET rats (AR/peak = 73 +/- 2 and 80 +/- 1 msec, respectively). The rate of intracellular Ca2+ decay and the integral of the Ca2+ transient through the entire contractile cycle were significantly longer in myocytes from SU than from ST rats (Ca2+ signal normalized to peak amplitude = 152 +/- 8 vs. 135 +/- 5 msec, respectively). Collectively, our data showed the presence of cardiomyocyte abnormalities in an insulin-resistant stage that precedes frank type 2 diabetes. Furthermore, metformin prevented the development of sucrose-induced insulin resistance and the consequent cardiomyocyte dysfunction.

Epinephrine enhancement of potassium-stimulated immunoreactive insulin secretion. Role of beta-adrenergic receptors.

Although epinephrine stimulates insulin release by activation of beta-adrenergic receptors, its dominant effect (mediated by stimulation of alpha-adrenergic receptors) is an inhibition of insulin secretion that is powerful enough to suppress the secretory activity of insulin's most potent stimulants. The insulin-secretory response to potassium chloride (KCl) infusion, however, is not suppressed; in fact, in ureter-ligated dogs simultaneously infused with 360 microgram. epinephrine per hour and 2 mEq. KCl per kilogram per hour, insulin release is actually increased about threefold (over controls). Propranolol blockade of beta-adrenergic receptors essentially abolishes the insulin response to KCl infusion, with and without epinephrine. It is unlikely that KCl, like epinephrine, provokes insulin release by direct stimulation of the beta-adrenergic receptors of the beta cells of the pancreatic islets. However, potassium in some way enhances the beta adrenergic (secretory) activity of epinephrine and blunts its usually dominant alpha-adrenergic (inhibitory) effect.

Suppression of sleep-induced growth hormone secretion by anticholinergic agent abolishes dawn phenomenon.

The dawn phenomenon was evaluated in eight C-peptide-negative type I (insulin-dependent) diabetic patients on two occasions by measuring glucose concentrations every 30 min from 2400 to 0800 h while the subjects were receiving an insulin infusion (0.12 mU.kg-1.min-1). In random order at 2230 h, they orally received either a sleeping medication alone or with 5.0 mg methscopolamine bromide, an anticholinergic agent. The peak growth hormone (GH) concentrations (ng/ml +/- SE) after sleep were markedly inhibited by methscopolamine (4.7 +/- 2.6 vs. 23.0 +/- 9.2). During the control night, the late (0400-0800 h) glucose response (area under curve but above 0400 h value) was significantly higher (P less than .02) than the early (2400-0400 h) glucose response (area under curve but above 2400 h value). After methscopolamine, the early and late glucose responses were virtually identical. The anticholinergic agent did not affect glucagon levels, overnight urinary catecholamine excretion, or the diurnal cortisol concentrations. The total area under the free fatty acid (FFA) curves was significantly (P less than .05) reduced by methscopolamine. We conclude that sleep-induced GH secretion may cause the dawn phenomenon by increasing FFA levels. Oral administration of methscopolamine at bedtime is a simple pharmacological approach that could test the clinical importance of the dawn phenomenon.

Application of a diabetes managed care program. The feasibility of using nurses and a computer system to provide effective care.

OBJECTIVE: Treatment of patients with diabetes often falls short of recommended process and outcome guidelines. To improve the quality of the provided diabetes care, a program (the Comprehensive Diabetes Care Service [CDCS]) using a computerizing tracking and recall system in conjunction with nurses following protocols was implemented in a managed care setting. The impact of this program was studied and compared to the care provided to patients in another managed care setting. RESEARCH DESIGN AND METHODS: Patients followed in the CDCS who completed a diabetes education course were compared with patients followed in a group model health maintenance organization (GMH) who also completed a diabetes education course. CDCS patients received routine care in the program. GMH patients came to the CDCS yearly to have a diabetes evaluation. A chart review was also performed on their GMH outpatient records. RESULTS: Initial HbA1c levels were higher in the CDCS group than in the GMH group (median of 11.9 vs. 10.0%). In the CDCS patients, HbA1c levels not only fell significantly but were also significantly lower (P < 0.05) than in the GMH patients during the 2nd and 3rd year of follow-up care. There were no significant changes in HbA1c levels in the GMH patients. When CDCS patients were divided into compliant and noncompliant patients, the median HbA1c levels in compliant patients was 8.2%, compared with 11.5% in the noncompliant group. The CDCS patients who needed treatment for hypercholesterolemia were more likely to have a lowering of their cholesterol levels than the GMH patients. All process measures, such as yearly measurement of HbA1c levels, lipid levels, and foot and retinal exams, occurred much more frequently in the CDCS patients. CONCLUSIONS: The system developed and implemented for managing diabetes improved both outcome and process measures. The comparison group, followed at another managed care setting, received the care consistent with the average (suboptimal) quality of care provided to patients with diabetes in the U.S. Therefore, by using innovative systems of management, the treatment of patients with diabetes can be greatly improved.

Effect of isocaloric substitution of chocolate cake for potato in type I diabetic patients.

Traditional dietary advice given to people with diabetes includes eliminating simple sugars (primarily sucrose) from the diet. Many people have difficulty following this recommendation. Because patients with type I (insulin-dependent) diabetes do not need overall calorie restriction, there is no caloric reason to restrict sucrose. In this study, we looked at the effect of the isocaloric substitution of a piece of chocolate cake for a baked potato in a mixed meal to determine whether this would increase the blood glucose in patients with type I diabetes. The glucose response to a cake-added meal was significantly greater than to a standard meal. The glucose response was no different between a cake-substitution meal and a standard meal. The reproducibility studies showed no difference between repeated standard meals. The urinary glucose excretion was significantly greater after a cake-added meal but was no different with the other pairs. There were no significant differences in the counterregulatory hormone responses at baseline between any of the paired studies. In conclusion, patients with type I diabetes may substitute a sucrose-containing dessert for another carbohydrate in their diet without compromising their postprandial glucose response. These data suggest that a dessert exchange may be helpful and not harmful in the management of diabetic patients. There is an inherent variability (at least 16%) in an insulin-requiring patient's response to a meal, making self-monitoring of blood glucose and adjustment of insulin doses necessary to achieve near euglycemia.

Cost-effective screening for diabetic retinopathy using a nonmydriatic retinal camera in a prepaid health-care setting.

OBJECTIVE: To assess the efficacy of using a nonmydriatic Polaroid retinal camera as a method for screening diabetic patients for treatable diabetic retinopathy. RESEARCH DESIGN AND METHODS: All 522 diabetic patients followed in a health maintenance organization-affiliated diabetes program had retinal photos taken. Compliance with the routine referral to one of two retinal specialists (the examiners) was 74%. The results from the examiners were compared with the results of the reader of the retinal photos. RESULTS: Sensitivity was 100% and specificity was 82% for the diagnosis of serious diabetic retinopathy (preproliferative or proliferative retinopathy or macular edema) by the examiners compared with the diagnosis of any diabetic retinopathy by the reader. No patient had serious diabetic retinopathy inside or outside the photographic field that was missed because all patients with serious diabetic retinopathy showed some diabetic retinopathy within the photographic field. The reader tended to underrate the severity of the diabetic retinopathy, but when the reader diagnosed serious diabetic retinopathy, it was always present on exam. CONCLUSIONS: The nonmydriatic retinal camera is easy to use, inexpensive, and can be used as part of a general diabetes exam, independent of a physician, in patients who should, but may not, be referred to an ophthalmologist. Any patient with abnormal findings on photos should be referred to an ophthalmologist, and any patient with findings of serious diabetic retinopathy on the photos should be referred immediately for possible laser therapy.

Simple solution to problem of biostator-induced insulin aggregation.

It has recently been reported that there is a significant loss of insulin immunoreactivity and bioavailability secondary to heat-induced insulin aggregation during prolonged insulin delivery by the Biostator. This artifact of Biostator insulin delivery system makes data generated by studies that use prolonged, continuous insulin infusions performed with the Biostator uninterpretable. We report the prevention of this problem by the addition of 20 ml heparinized whole blood to a 500-ml reservoir containing the insulin to be infused. The proposed solution is simple, economical, and without risk to the subject since his or her own blood can be used.

Diabetes and disenrollment in a health maintenance organization setting: a 4-year longitudinal study with a matched cohort.

OBJECTIVE: The increasing enrollment of Medicare beneficiaries in health maintenance organizations (HMOs) in recent years has caused concern about whether HMOs and their providers have created an unfavorable environment for members who are chronically ill. This study was designed to examine whether there are any differences in disenrollment rates among enrollees with diabetes and enrollees without diabetes. RESEARCH DESIGN AND METHODS: This was a 4-year longitudinal follow-up study with a matched cohort. Medicare beneficiaries (aged > or =65 years) with diabetes identified through pharmacy records in 1994 were matched with a comparison group according to age, sex, comorbidities, and type of provider groups in an HMO in California. RESULTS: The overall distribution of the characteristics of members in the diabetic and matched nondiabetic group is almost identical. The matched-pair chi2 tests indicated that there were no statistical differences in disenrollment rates between diabetic and nondiabetic members during all three follow-up periods (P = 0.16-0.85). CONCLUSIONS: We found that the HMO members with diabetes did not disenroll from the HMO at a higher rate than those without diabetes. The findings should alleviate some of the concern that HMOs and their contracted providers have created an unattractive environment for members who have chronic diseases such as diabetes.