Improvement of host response to sepsis by photobiomodulation

OBJECTIVE: To evaluate the correlation between predialysis glycemic control and clinical outcomes for type II diabetic patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Sixty type II diabetic patients on CAPD were classified into 2 groups according to the status of glycemic control. In group G (good glycemic control), more than 50% of blood glucose determinations were within 3.3-11 mmol/L and the glycosylated hemoglobin (HbA1C) level was within 5-10% at all times. In group P (poor glycemic control), fewer than 50% of blood glucose determinations were within 3.3-11 mmol/L or HbA1C level was above 10% at least once during the follow-up duration. In addition to glycemic control status, predialysis serum albumin, cholesterol levels, residual renal function, peritoneal membrane function, and the modes of glycemic control were also recorded. SETTING: Dialysis Unit, Department of Nephrology of a single university hospital. PATIENTS: From February 1988 to October 1995, 60 type II diabetic patients receiving CAPD for at least 3 months were enrolled. MAIN OUTCOME MEASURES: Morbidities before and during the dialysis period, patient survival, and causes of mortality. RESULTS: The patients with good glycemic control had significantly better survival than patients with poor glycemic control (p < 0.01). There was no significant difference in predialysis morbidity between the two groups. No significant differences were observed in patient survival between the patients with serum albumin greater than 30 g/L and those with less than 30 g/L (p = 0.77), with cholesterol levels greater or less than 5.18 mmol/L (p = 0.73), and with different peritoneal membrane solute transport characteristics evaluated by peritoneal equilibration test (p = 0.12). Furthermore, there was no significant difference in survival whether the patients controlled blood sugar by diet or with insulin (p = 0.33). Cardiovascular disease and infection were the major causes of death in both groups. Although good glycemic control predicts better survival, it does not change the pattern of mortality in diabetics maintained on CAPD. CONCLUSIONS: Glycemic control before starting dialysis is a predictor of survival for type II diabetics on CAPD. Patients with poor glycemic control predialysis are associated with increased morbidity and shortened survival.     

Effects of glycemic control on plasma 3-deoxyglucosone levels in NIDDM patients

OBJECTIVE: To clarify the effects of glycemic control on the level of 3-deoxyglucosone (3-DG), a reactive dicarbonyl compound, in plasma from diabetic patients. RESEARCH DESIGN AND METHODS: Fasting plasma samples were collected from 15 healthy volunteers and 27 patients with NIDDM. Samples were collected from six poorly controlled patients before and after improved glycemic control for at least 2 months. Plasma 3-DG was determined by high-performance liquid chromatography (HPLC) as a 2,3-diaminonaphthalene derivative. We observed the relationship of 3-DG levels with plasma glucose or HbA1c levels and examined changes in 3-DG levels after glycemic control in the six patients. RESULTS: Plasma 3-DG was significantly more increased in diabetic patients than in nondiabetic control subjects (31.8 +/- 11.3 vs. 12.8 +/- 5.2 ng/ml, means +/- SD, P < 0.001), but there was an approximately threefold difference in 3-DG levels among diabetic patients. 3-DG levels were well correlated with plasma glucose (r = 0.56, P < 0.005) and HbA1c levels (r = 0.74, P < 0.001) in diabetic patients. The improvement of hyperglycemia in six patients resulted in a significant decrease in 3-DG (35.2 +/- 13.2 vs. 21.3 +/- 3.4 ng/ml, P < 0.05). CONCLUSIONS: The results indicate that the plasma glucose level is a predominant determinant of the plasma 3-DG level in diabetic patients and good glycemic control would be important to reduce this reactive metabolite.     

Cloning and functional expression of a human liver organic cation transporter

OBJECTIVE: The triglyceride-lowering effects of omega-3 fats and HDL cholesterol-raising effects of exercise may be appropriate management for dyslipidemia in NIDDM. However, fish oil may impair glycemic control in NIDDM. The present study examined the effects of moderate aerobic exercise and the incorporation of fish into a low-fat (30% total energy) diet on serum lipids and glycemic control in dyslipidemic NIDDM patients. RESEARCH DESIGN AND METHODS: In a controlled, 8-week intervention, 55 sedentary NIDDM subjects with serum triglycerides > 1.8 mmol/l and/or HDL cholesterol < 1.0 mmol/l were randomly assigned to a low-fat diet (30% daily energy intake) with or without one fish meal daily (3.6 g omega-3/day) and further randomized to a moderate (55-65% VO2max) or light (heart rate < 100 bpm) exercise program. An oral glucose tolerance test (75 g), fasting serum glucose, insulin, lipids, and GHb were measured before and after intervention. Self-monitoring of blood glucose was performed throughout. RESULTS: In the 49 subjects who completed the study, moderate exercise improved aerobic fitness (VO2max) by 12% (from 1.87 to 2.07 l/min, P = 0.0001). Fish consumption reduced triglycerides (0.80 mmol/l, P = 0.03) and HDL3 cholesterol (0.05 mmol/l, P = 0.02) and increased HDL2 cholesterol (0.06 mmol/l, P = 0.01). After adjustment for age, sex, and changes in body weight, fish diets were associated with increases in GHb (0.50%, P = 0.05) and self-monitored glucose (0.57 mmol/l, P = 0.0002), which were prevented by moderate exercise. CONCLUSIONS: A reduced fat diet incorporating one daily fish meal reduces serum triglycerides and increases HDL2 cholesterol in dyslipidemic NIDDM patients. Associated deterioration in glycemic control can be prevented by a concomitant program of moderate exercise.     

Gastric myoelectrical activity in patients with diabetes. Role of glucose control and autonomic nerve function

OBJECTIVE: Gastric myoelectrical activity was studied in diabetic patients using electrogastrography (EGG) to elucidate the relationship between glucose control, diabetic autonomic neuropathy (AN), and gastrointestinal motility. RESEARCH DESIGN AND METHODS: Cutaneous EGG was recorded during 1 h of fasting and 1 h after the ingestion of a standard meal in 57 diabetic patients and 10 healthy subjects. EGG was measured in 12 diabetic patients after glycemic control for 4 weeks. Diabetic patients were also studied with respect to the presence of gastrointestinal symptoms and AN. RESULTS: The percentage of dominant electrical frequency (DF) in normal range (the percentage ratio between the power at 2.4-3.6 cycles/min [cpm] and at 1-10 cpm) was significantly lower in patients with AN than in either the control subjects or the patients without AN (P < 0.01). The dominant frequency instability coefficient (DFIC) was significantly higher in patients with and without AN than in the control subjects (P < 0.01). The postprandial-to-fasting power ratio (PR) was the lowest in patients with AN (P < 0.01). Multiple regression analysis revealed that HbA1c levels were independently associated with the DFIC (R2 = 0.099, P = 0.0170) and that AN and HbA1c levels were independently associated with the PR (R2 = 0.378, P < 0.0001) in diabetic patients. The percentage of normal DF increased and the DFIC decreased significantly after glycemic control in 12 diabetic patients (P = 0.0409; P = 0.0096, respectively). CONCLUSIONS: There appears to be an association between improvement in gastric myoelectrical activity and autonomic nerve function. Abnormalities of gastric myoelectrical activity may be partly ameliorated via the improvement of autonomic nerve function, which accompanies glycemic control.     

Plasma levels of pentosidine in diabetic patients: an advanced glycation end product

Nonenzymatic reactions between glucose and proteins yield advanced glycation end products (AGE) such as pentosidine. AGE accumulate in diabetic patients, alter the structure and function of tissue proteins, stimulate cellular response, and have thus been implicated in diabetic tissue damage. The present study was undertaken to assess the factors determining plasma total pentosidine level in diabetic patients and the possible relation between plasma pentosidine level and diabetic complications. In diabetic patients, including patients with renal failure, plasma pentosidine levels, assessed by HPLC assay, were correlated with serum creatinine (P < 0.0001). In patients with normal renal function, pentosidine levels were correlated with blood glucose control (hemoglobin Alc: P = 0.0028; fructoselysine: P = 0.0133), serum creatinine (P = 0.029), patient age (P = 0.0416), duration of diabetes (P = 0.0431), and total cholesterol (P = 0.0056) and LDL-cholesterol (P = 0.0208). Multiple regression analysis revealed an independent influence of hemoglobin Alc and serum creatinine on pentosidine levels (r2 = 0.216, P = 0.0026). Pentosidine levels were higher in patients with than in those without hypertension (P = 0.043) or ischemic heart diseases (P = 0.0061). No such differences were observed between patients with and without albuminuria or retinopathy. Multiple regression analysis revealed an independent influence of plasma pentosidine on the presence of hypertension (r2 = 0.129, P = 0.0382) and of plasma pentosidine and HDL-cholesterol on the presence of ischemic heart disease (r2 = 0.326, P = 0.0012). The present study demonstrated that plasma pentosidine level was significantly influenced by the quality of glycemic control and renal function. Pentosidine level was also correlated with hypertension and ischemic heart disease, and might be taken as a biomarker of diabetic cardiovascular risk.     

Measurement of cytotoxic T lymphocyte precursor frequencies reveals cryptic HLA class I mismatches in the context of unrelated donor bone marrow transplantation

OBJECTIVE: Type 2 diabetes is a slowly progressive disease, in which the gradual deterioration of glucose tolerance is associated with the progressive decrease in beta-cell function. Hyperglycemia per se has deleterious effects on both beta-cell function and insulin action, which are partially reversible by the short-term control of blood glucose levels. We hypothesized that the induction of euglycemia, using intensive insulin therapy at the time of clinical diagnosis, could lead to a significant improvement in insulin secretion and action and thus alter the clinical course of the disease. RESEARCH DESIGN AND METHODS: Thirteen newly diagnosed diet-unresponsive type 2 diabetic patients were treated with continuous subcutaneous insulin infusion (CSII) for 2 weeks and followed longitudinally while being treated with diet alone. RESULTS: Four patients were considered therapeutic failures since CSII failed to induce euglycemia (n = 1) or glucose control deteriorated within 6 months after CSII (n = 3). The remaining nine patients were maintained on diet alone with adequate control from 9 to > 50 months (median +/- SE, 26 +/- 4.8 months). In five patients, glycemic control deteriorated after 9-36 months, but a repeat 2-week CSII treatment reestablished control in four patients. One of these patients underwent a third CSII treatment 13 months later. At the time this article was written, six patients of the initial group were still controlled without medication 16-59 months (median +/- SE, 45.5 +/- 6.6 months) after the initiation of treatment. Body weight remained unchanged in all patients. CONCLUSIONS: These findings suggest that in a significant proportion of type 2 diabetic patients who fail to respond to dietary measures, short-term intensive insulin treatment can effectively establish responsiveness, allowing long-term glycemic control without medication. Further studies are required to establish whether simpler treatment regimens could be equally effective. If the hypothesis offered here finds support, present approaches to the management of newly diagnosed type 2 diabetes may need to be revised.     

Conrad Berens Lecture. The management of infectious keratitis as we approach the 21st century

We have assessed the capacity of continuous subcutaneous insulin infusion (CSII) to maintain good blood glucose metabolic control on Sundays, when waking is delayed, with reference to intensified conventional insulin therapy by multiple daily injections (MDI). The study lasted 3 weeks, including 3 week-ends. A total of 20 IDDM patients were selected for metabolic control: ten were treated by CSII and ten by MDI. Blood glucose was determined at least three times a day (fasting on waking, pre-lunch and pre-dinner). The times of blood glucose determinations and their values were recorded in a memory reflectance meter. Waking, the first blood glucose measurement and the first insulin injection (MDI) or bolus (CSII) were about 1 h later on Sundays than on a weekday (44 +/- 4 min in MDI group, P < 0.04; and 59 +/- 7 min in CSII group, P < 0.02). The times of the pre-lunch and pre-dinner blood glucose determinations were not significantly different. The mean waking and pre-lunch blood glucose values of the MDI group were higher on Sundays (11.5 +/- 3.8 and 9.7 +/- 4.5 mmol/l) than on weekdays (8.7 +/- 2.3 and 7.1 +/- 2.5 mmol/1)(P < 0.01). The pre-prandial blood glucose levels of the CSII group on Sundays and weekdays were not statistically different at any time. Changes in the waking time and the subsequent delay in the first insulin bolus on Sunday may alter blood glucose control in patients on MDI, but CSII allows such changes without any glycemic side effects.     

Molecular characterization of a single mitochondria-associated double-stranded RNA in the green alga Bryopsis

OBJECTIVE: To evaluate the effect of a moderate dose of fish oil on glycemic control and in vivo insulin action in type 2 diabetic men with elevated plasma triacylglycerols and to determine the effect of the same treatment on gene expression of GLUT4, lipoprotein lipase (LPL), and hormone-sensitive lipase (HSL) in the abdominal adipose tissue. RESEARCH DESIGN AND METHODS: A total of 12 type 2 diabetic men were randomly allocated to 2 months of 6 g daily of either fish oil or sunflower oil, separated by a 2-month washout interval, in a double-blind crossover design. RESULTS: For glucose metabolism, 2 months of fish oil supplementation compared with sunflower oil led to similar fasting plasma insulin, glucose, and HbA1c. Basal hepatic glucose production did not increase after fish oil. There was no difference in insulin suppression of hepatic glucose production nor in insulin stimulation of whole-body glucose disposal measured by the euglycemic-hyperinsulinemic clamp. Fish oil did not ameliorate the low mRNA level of GLUT4 in adipose tissue of these patients. For lipid profile, fish oil lowered plasma triacylglycerol more than sunflower oil (P < 0.05) and tended to increase the amount of mRNA of both LPL and HSL in adipose tissue. CONCLUSIONS: A moderate dose of fish oil did not lead to deleterious effects on glycemic control or whole-body insulin sensitivity in type 2 diabetic men, with preserved triacylglycerol-lowering capacities.     

Nonfasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes

OBJECTIVE: To evaluate the relative value of plasma glucose (PG) at different time points in assessing glucose control of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Glycemic profiles, i.e., PG at prebreakfast (8:00 A.M.), prelunch (11:00 A.M.), postlunch (2:00 P.M.), and extended postlunch (5:00 P.M.) times over the same day, were obtained in 66 type 2 diabetic patients on an ambulatory basis. The different time points of PG were compared with a measurement of HbA1c made in a reference laboratory. RESULTS: Extended postlunch PG was lower than prebreakfast PG (104 +/- 21 vs. 133 +/- 35 mg/dl, P < 0.02) in patients demonstrating good diabetic control (HbA1c < or = 7.0%), was not different from prebreakfast PG (149 +/- 47 vs. 166 +/- 26 mg/dl, NS) in patients demonstrating fair diabetic control (7.0% < HbA1c < or = 8.5%), and was higher than prebreakfast PG (221 +/- 62 vs. 199 +/- 49 mg/dl, P < or = 0.01) in those demonstrating poor diabetic control (HbA1c < or = 8.5%). Prebreakfast, prelunch, postlunch, and extended postlunch PG values were all significantly correlated with HbA1c. Multiple linear regression analysis demonstrated that postlunch PG and extended postlunch PG correlated significantly and independently with HbA1c, but that prebreakfast PG and prelunch PG did not. Moreover, postlunch PG and extended postlunch PG demonstrated better sensitivity, specificity, and positive predictive value in predicting poor glycemic control than did prebreakfast PG or prelunch PG. CONCLUSIONS: In type 2 diabetes, postlunch PG and extended postlunch PG are better predictors of glycemic control than fasting plasma glucose (FPG). We therefore suggest that they be more widely used to supplement, or substitute for, FPG in evaluating the metabolic control of type 2 diabetic patients.     

Blood glucose monitoring by diabetic adolescents: Compliance and metabolic control.

Evaluated a behavioral contract for self-monitoring of blood glucose (SMBG) compliance among diabetic adolescents, using reflectance meters with memory to assess the target behavior. 30 patients were randomized to either meter-alone or meter?+?contract (MPC) conditions; an additional 12 patients served in a conventional-therapy control group. Compliance for the meter-alone group declined sharply during the 16-wk intervention, but remained at or above baseline levels for the MPC group. Despite the large between-group differences in SMBG frequency, both groups showed moderate improvement in measures of diabetic control, suggesting that SMBG frequency had little impact on health status. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationship of blood thromboxane-B2 (TxB2) with lipid peroxides and effect of vitamin E and placebo supplementation on TxB2 and lipid peroxide levels in type 1 diabetic patients

OBJECTIVE: To study the effect of vitamin E supplementation on platelet hyperaggregability in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Written informed consent according to the Institutional Review Board on Human Experimentation guidelines was obtained from diabetic patients (n = 29) and their age-matched normal siblings (n = 21) to participate in this study. Diabetic patients were supplemented with DL-alpha-tocopherol (vitamin E) capsule (orally, 100 IU/day) or placebo for 3 months in a double-blind clinical trial. Alternate diabetic patients were assigned to vitamin E or placebo during regular visits to the clinic. Fasting blood was collected from each diabetic patient before the start and after the vitamin E or placebo supplementation. Platelet aggregability was assessed by competitive enzyme-linked immunosorbent assay of the blood TxB2 (a stable thromboxane metabolite). Plasma vitamin E and MDA (malondialdehyde, a product of lipid peroxidation) was assessed by high-performance liquid chromatography. Data were analyzed statistically on 12 diabetic patients on vitamin E and 12 on placebo supplementation. RESULTS: Diabetic patients (n = 29) had 62% higher (P < 0.05) levels of TxB2 and 15% higher levels (P < 0.05) of MDA in comparison to normal subjects (n = 21). Plasma TxB2 levels had a significant correlation with MDA levels (r = 0.45, P < 0.02) but not with the HbA1 (r = -0.08), glucose (r = -0.13), duration of diabetes (r = -0.04), or age (r = 0.12) of diabetic patients. Vitamin E supplementation lowered MDA levels by 30% (P < 0.04), TxB2 levels by 51% (P < 0.03), and triglyceride levels by 22% (P < 0.04) in diabetic patients. There were no differences in these parameters before versus after placebo supplementation. CONCLUSIONS: The elevated blood level of TxB2 (hyperaggregability of platelets) is significantly related to the level of lipid peroxidation products (oxidative stress) in type 1 diabetic patients. Supplementation of modest doses of vitamin E (100 IU/day) significantly lowers blood TxB2 and lipid peroxidation products levels in type 1 diabetic patients.     

Effect of obesity on the response to insulin therapy in noninsulin-dependent diabetes mellitus

An initial improvement in glycemic control is often followed by gradual deterioration of glycemia during insulin treatment of patients with noninsulin-dependent diabetes mellitus (NIDDM). We examined the causes of such worsening in a 12-month follow-up analysis of 100 insulin-treated NIDDM patients in the Finnish Multicenter Insulin Therapy Study who were treated with either combination therapy with insulin or insulin alone. In the entire study group, glycemic control averaged 9.7 +/- 0.2% at 0 months and 8.0 +/- 0.1%, 8.0 +/- 0.1%, 8.2 +/- 0.1%, and 8.5 +/- 0.2% at 3, 6, 9, and 12 months (P < 0.001 for each time point vs. 0 months). Glycemic control at 12 months was significantly worse than that at 3 (P < 0.001), 6 (P < 0.001), and 9 months (P < 0.02). Baseline body mass index was the most significant predictor of deterioration in glycemic control. During 1 yr, hemoglobin A1c decreased almost 3-fold more (by 1.7 +/- 0.2%; P < 0.001 vs. 0 months) in patients whose baseline weight was below the mean baseline body mass index of 28.1 kg/m2 (nonobese patients) than in those whose weight exceeded 28.1 kg/m2 (obese patients; 0.5 +/- 0.2%; P = NS vs. 0 months; P < 0.01 vs. obese patients). Glycemic control improved similarly over 1 yr in the nonobese subjects and deteriorated similarly in the obese patients regardless of their treatment regimen. Insulin doses, per body weight, were similar in the nonobese and obese patients. The nonobese patients consistently gained less weight during 12 months of combination therapy with insulin (3.5 +/- 0.6 kg at 12 months) than during insulin therapy alone (5.1 +/- 0.6 kg; P < 0.05). The treatment regimen did not influence weight gain in the obese group, who gained 4.4 +/- 1.0 kg during combination therapy with insulin and 4.5 +/- 1.1 kg during insulin therapy alone. We reached the following conclusions: 1) after an initial good response, glycemic control deteriorates more in obese than in nonobese patients with NIDDM; 2) in obese patients, weight gain per se cannot explain the poor glycemic response to combination or insulin therapy, but it may induce a disproportionately large increase in insulin requirements because of greater insulin resistance in the obese than in the nonobese; 3) in nonobese patients, glycemic control improves equally during 1 yr with combination therapy with insulin and insulin alone, but combination therapy with insulin is associated with less weight gain than treatment with insulin alone; 4) weight gain appears harmful, as it is associated with increases in blood pressure and low density lipoprotein cholesterol.     

Seven years of remission in a type I diabetic patient

OBJECTIVE: To analyze factors contributing to a long-term remission in a patient with type I diabetes. RESEARCH DESIGN AND METHODS: The patient was treated with cyclosporin for 16 mo after a short duration of symptoms. During the 7-yr follow-up, we tracked his glycemic control, oral glucose tolerance, insulin sensitivity, endogenous insulin secretion, and beta-cell immunology. The results are compared with those of matched diabetic patients and healthy control subjects. RESULTS: Insulin therapy was discontinued after 5 wk. Thereafter the patient had normal fasting and home blood glucose concentrations and near-normal HbA1c without insulin therapy for 7 yr. During this period, he maintained islet cell antibodies, although his basal and glucagon-stimulated C-peptide concentrations were normal. He participated in active physical training and had an insulin sensitivity higher than in sedentary control subjects or trained diabetic patients and equal to that in healthy athletes. His oral glucose tolerance decreased gradually and became diabetic during the last 3 yr. CONCLUSIONS: In this patient, an early start of cyclosporin therapy probably contributed to the maintenance of endogenous insulin secretion, and insulin sensitivity was high because of physical training. Consequently, the patient was able to maintain normoglycemia without exogenous insulin therapy for 7 yr.     

Breathing pattern and additional work of breathing in spontaneously breathing patients with different ventilatory demands during inspiratory pressure support and automatic tube compensation

OBJECTIVE: To identify predictors of hypoglycemic and hyperglycemic episodes in hospitalized patients with diabetes with special attention to the effectiveness of sliding scale insulin regimens. DESIGN: Prospective cohort study. SETTING: Urban university hospital. PARTICIPANTS: One hundred seventy-one adults with diabetes mellitus as a comorbid condition admitted consecutively to medical inpatient services during a 7-week period. MEASUREMENTS: Demographic, clinical, and laboratory data from inpatient medical records. MAIN OUTCOMES: Rates of hypoglycemic (capillary blood glucose, < or = 3.3 mmol/L [< or = 60 mg/dL]) and hyperglycemic (capillary blood glucose, > or = 16.5 mmol/L [> or = 300 mg/ dL]) episodes. RESULTS: Of the patients, 23% experienced hypoglycemic episodes, and 40% experienced hyperglycemic episodes. The overall rates of hypoglycemic and hyperglycemic episodes were 3.4 and 9.8 per 100 capillary blood glucose measurements, respectively. Independent predictors of hypoglycemic episodes included African American race (relative risk [RR], 2.13) and low serum albumin level (RR, 1.92 per 100-g/L decrease); corticosteroid use was associated with a reduced risk of hypoglycemic episodes (RR, 0.32; P < .05). Independent predictors of hyperglycemic episodes included female gender (RR, 1.67), severity of illness (RR, 1.22 per 10 Acute Physiology and Chronic Health Evaluation III units), severe diabetic complications (RR, 2.32), high admission glucose level (RR, 1.33 per 5.5 mmol/L), admission for infectious disease (RR, 2.14), and corticosteroid use (RR, 3.74; P < .05). Of 171 patients, 130 (76%) were placed on a sliding scale insulin regimen. When used alone, sliding scale insulin regimens were associated with a 3-fold higher risk of hyperglycemic episodes compared with individuals following no pharmacologic regimen (RRs, 2.85 and 3.25, respectively; P < .05). CONCLUSIONS: Suboptimal glycemic control is common in medical inpatients with diabetes mellitus. The risk of suboptimal control is associated with selected demographic and clinical characteristics, which can be ascertained at hospital admission. Although sliding scale insulin regimens are prescribed for the majority of inpatients with diabetes, they appear to provide no benefit; in fact, when used without a standing dose of intermediate-acting insulin, they are associated with an increased rate of hyperglycemic episodes.     

Comparisons of studies on diabetic complications hampered by differences in GHb measurements

OBJECTIVE: To compare glycated hemoglobin (GHb) values of the relationship between glycemic control and complications of diabetes from laboratories involved in long-term studies (Steno, Oslo, Stockholm, Diabetes Control and Complications Trial, and Link?ping.) RESEARCH DESIGN AND METHODS: Blood samples were collected from 25 subjects selected to represent the clinically relevant measurement range. Fresh whole-blood samples were distributed and analyzed within 4 days of sample collection. Pretreatment of samples and analyses of GHb were performed according to the routine method of each study's central or reference laboratory. Results from each laboratory were compared with the group mean, i.e., the mean of all results for each sample. RESULTS: Regression analyses with the group mean values as independent variables and results from each laboratory as dependent variables showed that Oslo's result had a slope significantly different from the group mean. Laboratories used by the DCCT, Oslo, and Steno studies gave, on average, 0.4, 0.4, and 0.7% higher HbA1c readings than the group mean, respectively, while HbA1c results from Link?ping and Stockholm were, on average, 0.6 and 1.0% lower, respectively. CONCLUSIONS: There were large differences in GHb values among laboratories participating in studies of diabetic complications. The present data offer a guide to the comparison of results from the studies and underscores the need for standardization of GHb measurements.     

Nighttime insulin kinetics and glycemic control in type 1 diabetes patients following administration of an intermediate-acting lispro preparation

OBJECTIVE: To determine insulin kinetics and overnight glycemic control after bedtime administration of a new intermediate-acting insulin preparation called neutral protamine lispro (NPL). RESEARCH DESIGN AND METHODS: We studied 12 patients with well-controlled type 1 diabetes. The study had a double-blind, randomized, crossover design. After a lead-in period of 10-14 days two experiments were carried out with an interval of 2-7 days. During these experiments overnight insulin kinetics and fasting blood glucose levels were studied after evening administration of NPH insulin and NPL. Blood glucose levels < 3.8 mmol/l were treated by means of a variable infusion of a 20% glucose solution. RESULTS: A trend toward a shorter time to peak insulin concentration was observed after administration of NPL (P = 0.07). No differences between NPH and NPL were detected in the total area under the curve (AUC) for insulin, in insulin levels before breakfast, or in glucose levels before breakfast (P = 0.5, 0.6, and 0.4, respectively). CONCLUSIONS: We detected no major differences between NPH and NPL in the total AUC for insulin, prebreakfast glucose levels, or prebreakfast insulin levels. Therefore, we conclude that NPH and NPL are equally effective in controlling overnight glycemia.     

Doxazosin prevents proteinuria and glomerular loss of heparan sulfate in diabetic rats

We examined whether blood pressure reduction or good glycemic control equally lower albuminuria by preventing glomerular loss of heparan sulfate and progression of glomerulosclerosis in streptozotocin-induced diabetic rats. We used doxazosin, and alpha 1-adrenergic blocker, to lower systemic blood pressure, and good glycemic control was achieved by insulin treatment. Rats were killed after 20 weeks of treatment. Doxazosin significantly lowered systolic pressure in diabetic rats; however, it had no effect in normal rats. Good glycemic control also lowered systolic pressure. In diabetic rats with good glycemic control, doxazosin had an additive effect on blood pressure. Glomerular heparan sulfate synthesis was significantly lower and urinary albumin excretion higher in diabetic than in normal rats. Both doxazosin treatment and good glycemic control normalized these abnormalities in diabetic rats. Insulin normalized plasma glucose and glycosylated HbA1 concentrations in diabetic rats, as did doxazosin. Significant increases in mesangial area and glomeruloscelerosis were observed in diabetic rats. Only good glycemic control normalized these pathological changes in all diabetic rats. Two-way factorial ANOVA showed an interaction between the effects of doxazosin and insulin on systolic pressure and plasma glucose. The data show that after 20 weeks of doxazosin treatment, albuminuria was reduced by 80%; however, this treatment had no significant effect on mesangial expansion or progression to glomerulosclerosis. Conversely, good glycemic control prevented all three of the preceding sequelae.     

High-fat versus high-carbohydrate enteral formulae: effect on blood glucose, C-peptide, and ketones in patients with type 2 diabetes treated with insulin or sulfonylurea

Recently, two commercial enteral formulae for diabetic patients have been made available in Spain: a high-complex-carbohydrate, low-fat formulation (HCF) and a low-carbohydrate formulation (RCF). This study compares the effects of the two enteral nutritional formulae in patients with non-insulin-dependent diabetes mellitus (type 2 diabetes) treated with sulfonylurea or insulin. Fifty-two type 2 diabetes patients were randomly assigned to receive one of the two enteral formulae. Test enteral formula breakfast (250 cc) were consumed at approximately 0900 h after routine medications (insulin or oral agents) had been taken. Venous blood samples were obtained during fasting, before medication, and at 30 and 120 min after the start of the meal. The glycemic response of patients to the HCF was significantly greater than to RCF, but lower than in the sulfonyl type 2 diabetes treated groups. The incremental glucose response was within acceptable levels except in insulin treatment type 2 diabetes patients given HCF. Glucose, insulin, and C-peptide responses were higher in HCF than RCF groups. Two-factor analysis of variance on mean increments of blood glucose and C-peptide from basal levels to 30 min show the type of enteral nutrition as the main factor (P = 0.0010 and P = 0.0005, respectively). The RCF formula supplies 50.0% of energy as fat and 33.3% as carbohydrates, so it may be a ketogenic diet. It was found that both ketone bodies were higher after RCF than after HCF ingestion, but without statistical significance. We conclude that the partial replacement of complex digestible carbohydrates with monounsaturated fatty acids in the enteral formulae for supplementation of oral diet may improve glycemic control in patients with type 2 diabetes. The long-term effects of enteral diets high in monounsaturated fatty acids need further evaluation in patients with type 2 diabetes.     

Endocrine mechanisms of stress-induced DHEA-secretion

Fetuses born after pregnancies complicated by diabetes display delayed pulmonary maturation as measured by the delayed appearance of biochemical indicators of pulmonary maturity (phosphatidylglycerol, lecithin/sphingomyelin ratio) and by the occurrence of hyaline membrane disease even in term gestations. We tested the hypothesis that poor maternal glycemic control is associated with delayed appearance of the biochemical markers of fetal pulmonary maturation. Consecutive diabetic pregnancies with documentation of maternal glycemic control and amniotic fluid analysis for PG were analyzed. Maternal glycemic control was defined as good if the mean blood glucose was < or = 5.8 mmol/L (105 mg/dl) and poor if > 5.8 mmol/L. The presence of amniotic fluid phosphatidylglycerol was considered an indicator of lung maturity. Hyaline membrane disease was defined by the criteria of Corbet et al. [J Pediatr 118:277-284, 1991]. A total of 621 diabetic pregnancies were analyzed (261 good glycemic control, 360 poor glycemic control). Phosphatidylglycerol was absent in 21% of good glycemic control vs. 31% of poor glycemic control pregnancies (P < 0.05). When stratified by gestational age, the risk of absence of phosphatidylglycerol was significantly higher in the poor glycemic control group (O.R. 1.83, 1.19-2.84). At 36-37.9 weeks, poor glycemic control pregnancies had significantly higher rates of absent phosphatidylglycerol (37% vs. 22%, O.R. 2.04, 1.1-3.9). All cases of hyaline membrane disease beyond 32 weeks gestation occurred in poor glycemic control pregnancies. There were no cases of hyaline membrane disease beyond 37.0 weeks gestation. We conclude that poorly controlled maternal glucose levels are associated with delayed appearance of phosphatidylglycerol in diabetic pregnancies. However, after 37.0 weeks of gestation, no significant neonatal pulmonary disease occurred.