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PubMed1998

Phosphotyrosine-protein-phosphatase and diabetic disorders. Further studies on the relationship between low molecular weight acid phosphatase genotype and degree of glycemic control.

We have studied a new sample of 276 NIDDM patients from the population of Penne (Italy). Comparison of the new data with those of 214 diabetic pregnant women from the population of Rome reported in a previous paper has shown that the pattern of association between low molecular weight acid phosphatase genotype and degree of glycemic control is similar in the two classes of diabetic patients. Among nonobese subjects the proportion of ACP1*A (the allele showing the lowest enzymatic activity) is lower in diabetic patients with high glycemic levels (mean value greater than 8.9 mmol/l) than in diabetic patients with a low glycemic level (mean value less than 8.9 mmol/l). Among obese subjects no significant association is observed between glycemic levels and ACP1. Among nonobese subjects the concentration of f isoform of ACP1 is higher in patients showing a high glycemic level than in patients showing a low glycemic level. No significant difference is observed for s isoform.

Acid Phosphatase↗

PubMed1998

Randomized study of two different target levels of glycemic control within the acceptable range in type 2 diabetes. Effects on well-being at 1 year.

OBJECTIVE: A randomized trial with 1-year follow-up was conducted in 23 general practices to study the relationship between target values for glycemic control and well-being in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 176 patients with type 2 diabetes, aged 40-75 years, were included. General practitioners were encouraged to make decisions according to a standardized step-up regimen until the target level of glycemic control was reached. The random allocation to a strict or a less strict target level of glycemic control (fasting capillary glucose < 6.5 or < 8.5 mmol/l), change in HbA1c and fasting glucose, and initiating insulin or treatment with oral hypoglycemic agents were studied as putative determinants of scores on a type 2 diabetes symptom checklist, a profile of mood states, an affect balance scale, and general well-being. Adjustments were made for baseline scores on the outcome at issue. RESULTS: Positive affect (an odds ratio [OR] [95% CI] of 0.39 [0.19-0.83]) and perceived treatment burden (OR 0.48 [0.23-0.98]) were unfavorably altered in the group randomly allocated to stricter target levels (fasting capillary glucose < 6.5 mmol/l). Patients who had a decrease in HbA1c of 1% or more tended to have comparatively favorable mood (OR displeasure score 0.35 [0.13-0.94]) and general well-being scores at 1 year (ORs of having unfavorable scores ranged from 0.4 to 0.5, NS). CONCLUSIONS: Perceived treatment burden and positive effect are unfavorably affected by random allocation to a strict target level for glycemic control. Improved glycemic control is associated with favorable mood and possibly general well-being in type 2 diabetes.

Adult↗

PubMed2002

Are recurrent pregnancies a risk in Type 1 diabetes?

OBJECTIVE: To assess the significance of recurrent pregnancies for the progression of Type 1 diabetes as well as the glycemic level and the occurrence of pre-eclampsia in consecutive pregnancies of the same Type 1 diabetic women. METHODS: A retrospective population-based birth cohort from the years 1986-95, comprising data of all (n = 210) Type 1 diabetic mothers and their 296 births in a geographically defined catchment area. Of the 125 primiparous women, 46 had their first two pregnancies during the study period. The courses of their first and second pregnancies were compared to determine the level of glycemic control and the occurrence and recurrence of complications, such as pre-eclampsia and aggravated retinopathy. The characteristics of the 53 women who remained primiparous were evaluated. RESULTS: Retinopathy was aggravated more often during the first pregnancy (95% CI 0.1-1.0), but its incidence did not increase further by the beginning of the second pregnancy. Pre-eclampsia complicated 16.9% of all pregnancies: it was more common during the first than second pregnancy (95% CI 0.3-1.5) and its occurrence increased with the increasing severity of diabetes. Glycemic control was better in the second pregnancy, including both the periconceptional period (95% CI 0.7-2.8) and the later stages of pregnancy (95% CI 1.1-4.7). The women in the White classes F/R most often remained primiparous. CONCLUSIONS: Retinopathy was aggravated most often during the first pregnancy, but its infrequent occurrence in the second pregnancy reflects the reversible nature of these changes. The significance of the past pregnancy experience contributed to the increased tendency for optimal glycemic control in the second pregnancy.

Adult↗

PubMed2004

Impact of adjunctive thiazolidinedione therapy on blood lipid levels and glycemic control in patients with type 2 diabetes.

OBJECTIVE: This study was undertaken to assess the effect of pioglitazone hydrochloride and rosiglitazone maleate on blood lipid levels and glycemic control when these drugs are used as adjunctive therapy in type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes receiving metformin and/or sulfonylurea (n = 829) were evaluated in this national, multicenter, retrospective study. Medical records from 318 endocrinology practices in the USA were randomly selected and screened for study inclusion. Data related to patient demographics and laboratory data were extracted from medical records and analyzed for primary and secondary outcomes. MAIN OUTCOME MEASURES: The primary study outcome was the mean change in plasma rosiglitazone was associated with no significant triglyceride (TG) levels. Secondary outcome measures included mean changes in total cholesterol (TChol), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) concentrations and hemoglobin A1C levels. RESULTS: With pioglitazone, TG levels declined by a mean of 51.5 mg/dl (P < 0.001), HDL-C levels rose by 3.3mg/dl (P < 0.001), and no change was seen in LDL-C or TChol. Treatment with change in TG levels and a 1.5mg/dl mean increase in HDL-C (P < 0.001). Furthermore, rosiglitazone therapy was associated with an 8 mg/dl mean increase in TChol (P < 0.001), and a 5.8 mg/dl mean increase in LDL-C (P < 0.001). Hemoglobin A1C levels were significantly reduced by approximately 1% within thiazolidinedione (TZD) cohorts (P < 0.001), but were not significantly different between study groups (P = 0.257). CONCLUSIONS: Results from this study suggest that pioglitazone has a more favorable effect on lipid profiles of patients with type 2 diabetes compared with rosiglitazone. In particular, differences were observed in TG and LDL-C levels. Both TZDs were equivalent at reducing hemoglobin A1C levels. These differences in lipid effects may have an impact on cardiovascular outcomes. The full clinical importance of these lipid alterations must be further assessed in prospective trials.

Adult↗

PubMed2002

Effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus: a retrospective review of randomly selected medical records.

BACKGROUND: The antihyperglycemic effects of pioglitazone hydrochloride and rosiglitazone maleate are well documented. The results of clinical trials and observational studies have suggested, however, that there are individual differences in the effects of these drugs on blood lipid levels. OBJECTIVE: The present study evaluated the effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus. METHODS: This was a retrospective review of randomly selected medical records from 605 primary care practices in the United States in which adults with type 2 diabetes received pioglitazone or rosiglitazone between August 1, 1999, and August 31, 2000. The outcome measures were mean changes in serum concentrations of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glycosylated hemoglobin (HbA1c) values. RESULTS: Treatment with pioglitazone was associated with a reduction in mean TG of 55.17 mg/dL, a reduction in TC of 8.45 mg/dL, an increase in HDL-C of 2.65 mg/dL, and a reduction in LDL-C of 5.05 mg/dL. Treatment with rosiglitazone was associated with a reduction in mean TG of 13.34 mg/dL, an increase in TC of 4.81 mg/dL, a reduction in HDL-C of 0.12 mg/dL, and an increase in LDL-C of 3.56 mg/dL. With the exception of HDL-C, the differences in mean changes in lipid parameters between treatment groups were statistically significant (P < 0.001, pioglitazone vs rosiglitazone). Reductions in HbA1c were statistically equivalent between treatments (1.04% pioglitazone, 1.18% rosiglitazone). CONCLUSIONS: Treatment with pioglitazone was associated with greater beneficial effects on blood lipid levels than treatment with rosiglitazone, whereas glycemic control was equivalent between the 2 treatments.

Adult↗

PubMed2001

Self-monitoring of blood glucose levels and glycemic control: the Northern California Kaiser Permanente Diabetes registry.

PURPOSE: We sought to evaluate the effectiveness of self-monitoring blood glucose levels to improve glycemic control. SUBJECTS AND METHODS: A cohort design was used to assess the relation between self-monitoring frequency (1996 average daily glucometer strip utilization) and the first glycosylated hemoglobin (HbA1c) level measured in 1997. The study sample included 24,312 adult patients with diabetes who were members of a large, group model, managed care organization. We estimated the difference between HbA1c levels in patients who self-monitored at frequencies recommended by the American Diabetes Association compared with those who monitored less frequently or not at all. Models were adjusted for age, sex, race, education, occupation, income, duration of diabetes, medication refill adherence, clinic appointment "no show" rate, annual eye exam attendance, use of nonpharmacological (diet and exercise) diabetes therapy, smoking, alcohol consumption, hospitalization and emergency room visits, and the number of daily insulin injections. RESULTS: Self-monitoring among patients with type 1 diabetes (> or = 3 times daily) and pharmacologically treated type 2 diabetes (at least daily) was associated with lower HbA1c levels (1.0 percentage points lower in type 1 diabetes and 0.6 points lower in type 2 diabetes) than was less frequent monitoring (P < 0.0001). Although there are no specific recommendations for patients with nonpharmacologically treated type 2 diabetes, those who practiced self-monitoring (at any frequency) had a 0.4 point lower HbA1c level than those not practicing at all (P < 0.0001). CONCLUSION: More frequent self-monitoring of blood glucose levels was associated with clinically and statistically better glycemic control regardless of diabetes type or therapy. These findings support the clinical recommendations suggested by the American Diabetes Association.

Adult↗

PubMed1987

Polymorphonuclear cell derangements in type I diabetes.

Polymorphonuclear cell function had been studied in 58 Type I diabetic subjects. Chemotaxis, phagocytosis, adherence, bactericidal activity, NBT reduction capacity were evaluated. We enumerated gamma Fc receptor bearing polymorphonuclear cells and the percentage of immune complexes containing polymorphonuclear cells. These data were studied in accordance with glycemic levels and the presence of infections. All polymorphonuclear functions were decreased compared to non-diabetic subjects with the exception of phagocytosis. The efficiency of the diabetic sera on normal subjects polymorphonuclear cells was decreased (bactericidal activity, chemotactic index and phagocytosis). These abnormalities were independent of the presence of infection. No correlation was found with glycemic level. The percentage of cells bearing an Fc gamma receptor was less in diabetics than in normal (70.1 +/- 17.4 vs 80.2 +/- 7.8%). The percentage of immune complexes containing polymorphonuclear cells was increased (n = 16, 9.06 +/- 4.7 vs 4.75 +/- 2.1% in normals). There again, these data are without correlation with the presence of infections or glycemic level.

Adolescent↗

PubMed1995

Growth charts, growth velocity and bone development in childhood obesity.

OBJECTIVE: To compare the growth charts of obese subjects (4-18 years) with the Tanner's growth curves and to analyze the growth velocities and bone age of obese children in prepuberty and adolescence. Moreover to compare the relationship between the serum insulinemic and glycemic levels and height standard deviation score (HSDS). DESIGN: Growth charts: this study included 1250 obese subjects (669 males, 581 females) observed between 1981 and 1993 and divided into seven age categories (4-6, 7-8, 9-10, 11-12, 13-14, 15-16, 17-18 years). Growth velocities: yearly growth velocities of 579 obese subjects (325 males, 254 females) were compared to growth velocities of 473 controlled children of the same sex, chronological age and pubertal stage. Bone age (BA) of 846 obese subjects (470 males, 376 females) was estimated. Blood analysis: insulin secretion of 70 obese children was considered and compared to 70 lean controls of equal chronological age and sex. MEASUREMENTS: Growth rate, standardized height and other physical characteristics of the children were measured by trained examiners. All subjects were evaluated singularly for at least 4 years with a follow-up every 6 months. BA was estimated by radiograph of the left hand and wrist using the Tanner-Whitehouse II system by a single observer. For the insulin secretion study and glycemic levels oral glucose tolerance test (OGTT) was performed using a glucose load of 1.75 g/kg per body weight. Plasma insulin was assessed by a double antibody radioimmunoassay. RESULTS: In adipose children the growth charts, referred to 97th centile, 50th centile and 3rd centile, were superior to those of the normal population up to the age of 13 and 12.5 years for male and for female respectively; growth decreases at the above age in both sexes. The obese subjects were equal in height to the non obese subjects as they reached their 18th birthday. The growth velocity (cm/yr) of the obese child, in the age range considered here, does not show differences when compared with the lean child in the prepubertal status (P not significant) but decreases during Tanner's stage II, III IV in boys and girls (P < 0.0001). BA is more advanced over chronological age (delta BA-CA) in both sexes. The increase of BA over CA does not show a remarkable difference during pubertal maturation in boys (P not significant); whereas in girls the delta BA-CA decreases with advancing sexual maturation (P < 0.0001). Our obese subjects have significantly higher plasma insulinemic levels compared with the lean controls (P < 0.0001). Moreover there is a positive correlation between plasma insulinemic levels and HSDS (r = 0.881, P < 0.0001). We did not observe a correlation between serum glycemic levels and HSDS. CONCLUSION: Our data demonstrate that the growth increase in an obese child starts in the first years of life. The statural advantage acquired in the first years of life would be exploited and maintained up to the beginning of puberty and with a growth velocity equal to that of the lean subject. Skeletal maturation is strongly increased in both sexes. Bone age remained advanced during the entire period of pubertal development. During puberty obese subjects demonstrate a less notable growth spurt when compared with lean subjects. The growth advantage gradually decreases and final adult height of obese and normal subjects is equal.

Adolescent↗

PubMedDate not supplied

[Glycemia as a risk factor of reduced tolerance of hypoxic hypoxia in flight personnel].

The glycemic level was measured in 61 people exposed to hypoxic hypoxia. Three major types of glycemic responses were identified: type I--no change (15.79%); type II--hypoglycemia (49.12%), and type III--hyperglycemia (35.09%). The subjects with a low resistance to hypoxic hypoxia typically showed a low glycemic level (57.5 +/- 2.5 mg%. P < 0.05). It is suggested that three types of glycemic responses to hypoxia reflect three major pathways of biochemical adaptation of the body. It is recommended to study hormonal changes in people with hyperglycemic responses to hypoxia. This will help determine hormonal levels responsible for hyperglycemia and, consequently, develop methods of early detection of susceptibility to cardiovascular diseases and diabetes mellitus. This approach may contribute to medical expertise and rehabilitation of the flying personnel.

Adult↗

PubMedDate not supplied

Motor cortical excitability remains unaffected of short-term hyperglycemia in Type 1 diabetic patients.

BACKGROUND: In diabetic patients, hyperglycemia may precipitate seizures, and in experimental diabetes, indications for an increased neuronal excitability have been found. In this study, the excitability of the motor cortex and conduction of the central motor pathways were studied in diabetic patients in relation to the glycemic level. METHODS: Using a double-blind study protocol, transcranial magnetic stimulation (TMS) was performed in five Type 1 diabetic patients during normo- and hyperglycemia, using a hyperglycemic clamp technique. Single and paired-pulse transcranial magnetic and single root stimulations were applied before and after 3 h of a fixed glucose level of 5 and 16 mmol/l. The percentage of change from baseline at the two glycemic levels was calculated and compared. RESULTS: No difference in central motor conduction time was found comparing the change following normo- and hyperglycemia. Furthermore, no difference was observed for the changes in latency and amplitude following double stimulation with interstimulation intervals (ISIs) of 0-125 ms comparing normo- and hyperglycemia. CONCLUSIONS: The excitability of motor cortex and central motor nerve conduction in Type 1 diabetic patients are unaffected by short-term moderate hyperglycemia as compared with normoglycemia.

Adult↗

PubMed1997

Excursion of daily glucose profiles in pregnant women with IDDM: relationship with perinatal outcome.

The relationship between perinatal outcome and daily glucose profile throughout pregnancy was assessed in 31 White Class B through R pregnant diabetic women. The study population was divided into two groups on the basis of perinatal outcome: 20 patients (Group I) without neonatal complications; 11 patients (Group II) with at least one form of neonatal complications. The overall capillary blood glucose average levels of Group I (98.53 +/- 22.33 mg/dl) and of Group II (110.14 +/- 20.77 mg/dl) was significantly different (ANOVA p < 0.0001). From the first trimester of pregnancy Group I showed significantly lower mean glycemic levels for daytime, evening and night (Bonferroni test p < 0.05) than Group II and both presented daily glycemic profiles with very extensive excursions. During the second trimester the groups continued to maintain these differences in mean glycemic levels (Bonferroni test p < 0.05) but a daily glycemic rthythm with relative nocturnal hypoglycemia with closer fluctuations. In contrast, during the third trimester the two groups presented both a daily rhythm of glucose and glycemic values for daytime, evening and night not statistically different (Bonferroni test p < 0.06). The distribution of women according to glucose levels reached during the night showed a mode of distribution in both Group I and II collocated in a range 70-100 mg/dl. These findings suggest that an optimum perinatal outcome can be achieved only if the pre-pregnancy diabetic women can achieve a metabolic equilibrium during the second trimester which matches the daily excursions of glycemia present in a non-diabetic pregnant women avoiding individual episodes of night-time hypoglycemia.

Adult↗

PubMed2000

Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: A randomized trial. Arterial Disease Multiple Intervention Trial.

CONTEXT: Although niacin increases low levels of high-density lipoprotein cholesterol (HDL-C), which frequently accompany diabetes, current guidelines do not recommend use of niacin in patients with diabetes because of concerns about adverse effects on glycemic control; however, this is based on limited clinical data. OBJECTIVE: To determine the efficacy and safety of lipid-modifying dosages of niacin in patients with diabetes. DESIGN AND SETTING: Prospective, randomized placebo-controlled clinical trial conducted in 6 clinical centers from August 1993 to December 1995. PARTICIPANTS: A total of 468 participants, including 125 with diabetes, who had diagnosed peripheral arterial disease. INTERVENTIONS: After an active run-in period, participants were randomly assigned to receive niacin (crystalline nicotinic acid), 3000 mg/d or maximum tolerated dosage (n = 64 with diabetes; n = 173 without diabetes), or placebo (n = 61 with diabetes; n = 170 without diabetes) for up to 60 weeks (12-week active run-in and 48-week double-blind). MAIN OUTCOME MEASURES: Plasma lipoprotein, glucose, hemoglobin A(1c) (HbA(1c)), alanine aminotransferase, and uric acid levels; hypoglycemic drug use; compliance; and adverse events, in patients with diabetes vs without who were receiving niacin vs placebo. RESULTS: Niacin use significantly increased HDL-C by 29% and 29% and decreased triglycerides by 23% and 28% and low-density lipoprotein cholesterol (LDL-C) by 8% and 9%, respectively, in participants with and without diabetes (P<.001 for niacin vs placebo for all). Corresponding changes in participants receiving placebo were increases of 0% and 2% in HDL-C and increases of 7% and 0% in triglycerides, and increases of 1% and 1% in LDL-C. Glucose levels were modestly increased by niacin (8.7 and 6.3 mg/dL [0.4 and 0.3 mmol/L]; P =.04 and P<.001) in participants with and without diabetes, respectively. Levels of HbA(1c) were unchanged from baseline to follow-up in participants with diabetes treated with niacin. In participants with diabetes treated with placebo, HbA(1c) decreased by 0.3% (P =.04 for difference). There were no significant differences in niacin discontinuation, niacin dosage, or hypoglycemic therapy in participants with diabetes assigned to niacin vs placebo. CONCLUSIONS: Our study suggests that lipid-modifying dosages of niacin can be safely used in patients with diabetes and that niacin therapy may be considered as an alternative to statin drugs or fibrates for patients with diabetes in whom these agents are not tolerated or fail to sufficiently correct hypertriglyceridemia or low HDL-C levels. JAMA. 2000;284:1263-1270

Aged↗

PubMed1986

The Diabetes Control and Complications Trial (DCCT). Design and methodologic considerations for the feasibility phase. The DCCT Research Group.

The Diabetes Control and Complications Trial (DCCT) is a randomized, controlled clinical trial designed to assess the relationship between glycemic control and the development, progression, or amelioration of early vascular complications in persons with insulin-dependent diabetes mellitus (IDDM). The DCCT consists of two parallel studies: a primary prevention study and a secondary intervention study. The principal outcome in the primary prevention study is the initial appearance and subsequent progression of background retinopathy. In the secondary intervention study, the principal outcome is the progression or amelioration of preexistent minimal retinopathy. Subjects are randomly assigned to receive either experimental or standard therapy. Experimental therapy involves the use of an intensive insulin regimen designed to maintain near-normal glycemic levels in the absence of severe hypoglycemia. Standard treatment is designed to maintain near-normal glycemic levels in the absence of severe hypoglycemia. Standard treatment is designed to maintain subjects free of clinical symptoms related to hyper- or hypoglycemia while receiving up to two insulin injections daily. Two hundred seventy-eight volunteers have been enrolled in 21 centers in the United States and Canada in a preliminary study to assess the feasibility of conducting a full-scale, long-term clinical trial. Based on an external review of the feasibility study results, the DCCT will be expanded to include over 1400 subjects treated for a period of up to 10 yr. This article describes the DCCT and the considerations that led to the choice of specific design features for the feasibility phase.

Adolescent↗

PubMed2000

Effect of aproteic diet and fasting on insulin, pancreatic noradrenaline and luteinizing hormone. Changes after 24-hour refeeding.

OBJECTIVE AND DESIGN: the objective of this study performed in adult male rats was to determine the alteration in glycemic, insulin and gonadotrophin luteinizing hormone secretion, and noradrenaline pancreatic concentration caused by fasting (F) and aproteic diet (Ap) during 7 and 21 days respectively, as well as the recovery after 24-hour refeeding with control diet (Co). RESULTS: a significant decrease in glycemic levels was only achieved through fasting (F: 86 +/- 5.1 mg %), when compared with controls (Co: 107 +/- 5 mg %). In spite of the high levels of carbohydrates (89%) present in the aproteic diet, the animals fed with this diet showed no differences in glycemic levels (Ap: 120.3 +/- 12.2 mg %), compared with controls. As a result of fasting and aproteic diet, there was a significant decrease in insulin (F: 8.67 +/- 1.36; Ap: 5.7 +/- 0.67; Co: 31 +/- 3.4 uU/ml) and LH levels (F: 10.175 +/- 1.74; Ap: 13.7 +/- 4; Co: 29.83 +/- 4.91 ng/ml). The refed recovered insulin (FR: 50.57 +/- 6.63; ApR: 43.5 +/- 6.85 uU/ml), but not LH levels (FR: 14.25 +/- 3.54; ApR: 13.03 +/- 4.25 ng/ml). A significant increase was observed in the pancreatic noradrenaline concentration (P<0.001) of rats receiving aproteic diet (889.9 +/- 34.65 ng/mg tissue) and fasting during 7 days (827.5 +/- 55.7 ng/mg tissue), compared with controls (531.1 +/- 48.6 ng/mg tissue). CONCLUSIONS: fasting and aproteic diets altered gonadal and metabolic control. When returning to a normal nutritional condition, only the metabolic control, not the reproductive function, could be recovered in the first 24 hours of refeeding. Malnutrition-induced hypoinsulinemia would be caused by an increase in a specific noradrenergic tone.

Journal Article↗

PubMed2005

Humoral methylglyoxal level reflects glycemic fluctuation.

OBJECTIVES: According to the nonenzymatic glycation hypothesis, excessive production of toxic alpha-oxoaldehydes is associated with diabetes tissue damage. The aim of this study was to examine the hypothesis that methylglyoxal overproduction is affected by glycemic fluctuation. DESIGN AND METHODS: Methylglyoxal was measured by HPLC in 41 patients with diabetes, and correlated with 9-point daily glucose profiles, fasting glucose level, as well as early (HbA1c) and advanced glycation products. The 24-h glycemia variability was expressed as the M value, a quantitative index of diurnal glucose fluctuation. RESULTS: Methylglyoxal was, in parallel, analyzed in the whole blood and the plasma of the same individual. Significantly higher concentrations were measured in plasma samples of both, patients with diabetes (n=41) (742+/-141 vs. 409+/-131 nmol/L; P=0.000001) and normoglycemic controls (n=10) (520+/-42 vs. 338+/-62 nmol/L; P=0.0002). Difference between plasma and whole blood methylglyoxal (DeltaMG) in the same individual showed higher DeltaMG values in patients with diabetes (346+/-165 vs. 167+/-86 nmol/L; P=0.0027). Elevated methylglyoxal production was observed in patients with M values>20, yielding a significant correlation between M values and methylglyoxal levels. A significant negative correlation between methylglyoxal and creatinine clearance was observed (r=-0.38, P=0.019). CONCLUSIONS: Methylglyoxal was demonstrated to be a parameter characterized by high sensitivity to glycemic fluctuation. The difference between plasma and whole blood concentrations, in the diabetic population versus control subjects might be associated with increased biogenesis, less efficient endogenous detoxification and/or decreased elimination.

Adolescent↗

PubMedDate not supplied

The rescue effect of 15-deoxyspergualin on intraperitoneal microencapsulated xenoislets.

Because the development of surface neogrowth composed mainly of macrophages and fibroblasts precedes the recurrence of hyperglycemia in treated diabetic animals, the pericapsular macrophages may adversely affect the graft function of i.p. alginate-poly-L-lysine-alginate (A-P-A) microencapsulated islets. In order to clarify the role of pericapsular macrophages on late islet xenograft dysfunction, we investigated whether 15-deoxyspergualin (15-DSG), a macrophage inhibitor, has a rescue effect on the recurrent hyperglycemia in streptozotocin-induced diabetic mice that had been treated with i.p. transplantation of A-P-A microencapsulated rat islets. The mean duration of normoglycemia (whole blood glucose level below 8.3 mmol/l) in streptozotocin-induced diabetic mice treated with implantation of about 2200-2400 of A-P-A microencapsulated rat islets was 75 days. When the blood glucose levels were higher than 11.1 mmol/l for two consecutive determinations, 15-DSG at a dose of 0.625 mg/kg body weight or isotonic sodium chloride solution (control group) was given daily s.c.. The blood glucose levels decreased significantly from 13.9 +/- 0.5 mmol/l to 11.0 +/- 1.3 mmol/l (n = 18, p < 0.05) at the fourth day and to 7.6 +/- 1.0 mmol/l (n = 18) at the 14th day of 15-DSG administration. That was not significantly different from the mean glycemic level during the normoglycemic period (7.6 +/- 1.0 vs. 7.0 +/- 1.7 mmol/l, n = 18, p = NS). Isotonic sodium chloride solution injections did not reduce glycemic levels of mice in the control group. As another control, 10 streptozotocin-induced diabetic mice were given the same daily doses of 15-DSG for 14 days. 15-DSG did not decrease the blood glucose levels of diabetic mice in the control group. We further studied the effect of 15-DSG on the expression of interleukin-1beta (IL-1beta) in peritoneal exudate mononuclear cells (PEMCs) using reverse transcription-polymerase chain reaction. It was found that the mRNA of IL-1beta was undetectable in PEMCs of 15-DSG-treated diabetic mice even after those cells were stimulated by lipopolysaccharides in vitro. Administration of 15-DSG at a daily dose of 0.625 mg/kg body weight from the 22nd to the 28th day after transplantation and 7 consecutive days every 3 weeks thereafter did not prolong graft survival of i.p. microencapsulated rat islets. Our data suggest that 15-DSG has a rescue effect when A-P-A microencapsulated islets have induced cellular overgrowth that threatens the survival of the graft. It is possible that the surface overgrowth composed of macrophages is involved in the pathophysiology of late failure of A-P-A microencapsulated xenogeneic islets.

Alginates↗

PubMed1999

Immediate feedback of HbA1c levels improves glycemic control in type 1 and insulin-treated type 2 diabetic patients.

OBJECTIVE: Accurate and reliable HbA1c results can be obtained at the time of the office visit by using benchtop analyzers. We tested the hypothesis that immediately available HbA1c results could improve glycemic control by changing physician or patient behavior or both. RESEARCH DESIGN AND METHODS: A randomized controlled trial was conducted in 201 type 1 and insulin-treated type 2 diabetic patients attending an academic diabetes center. HbA1c levels, changes in insulin therapy, and use of health care resources were assessed during a 12-month follow-up period. RESULTS: HbA1c levels decreased significantly at 6 and 12 months in the immediate assay group (-0.57 +/- 1.44 and -0.40 +/- 1.65%, respectively; P < 0.01) but did not change in the control group (-0.11 +/- 0.79 and -0.19 +/- 1.16%, respectively; NS). The changes were similar for both type 1 and type 2 diabetic patients. There were no differences in the rates of hypoglycemic events or use of health care resources. CONCLUSIONS: In the setting of a controlled randomized trial, the immediate feedback of HbA1c results at the time of patient encounters resulted in a significant improvement of glycemic control at 6-month follow-up and persisted for the 12-month study. The introduction of this assay was positively received by both patients and physicians.

Blood Glucose↗

PubMed2003

Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study.

CONTEXT: The Diabetes Control and Complications Trial (DCCT) demonstrated the benefits of intensive treatment of diabetes in reducing glycemic levels and slowing the progression of diabetic nephropathy. The DCCT cohort has been examined annually for another 8 years as part of the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. During the EDIC study, glycemic levels no longer differed substantially between the 2 original treatment groups. OBJECTIVE: To determine the long-term effects of intensive vs conventional diabetes treatment during the DCCT on kidney function during the EDIC study. DESIGN, SETTING, AND PARTICIPANTS: Observational study begun in 1993 (following DCCT closeout) in 28 medical centers in the United States and Canada. Participants were 1349 (of 1375) EDIC volunteers who had kidney evaluation at years 7 or 8. MAIN OUTCOME MEASURES: Development of microalbuminuria, clinical-grade albuminuria, hypertension, or increase in serum creatinine level. RESULTS: Results were analyzed by intention-to-treat analyses, comparing the 2 original DCCT treatment groups. New cases of microalbuminuria occurred during the EDIC study in 39 (6.8%) of the participants originally assigned to the intensive-treatment group vs 87 (15.8%) of those assigned to the conventional-treatment group, for a 59% (95% confidence interval [CI], 39%-73%) reduction in odds, adjusted for baseline values, compared with a 59% (95% CI, 36%-74%) reduction at the end of the DCCT (P<.001 for both comparisons). New cases of clinical albuminuria occurred in 9 (1.4%) of the participants in the original intensive-treatment group vs 59 (9.4%) of those in the original conventional-treatment group, representing an 84% reduction in odds (95% CI, 67%-92%), compared with a reduction of 57% (95% CI, -1% to +81%) at the end of the DCCT. Fewer cases of hypertension (prevalence at year 8, 29.9% vs 40.3%; P<.001) developed in the original intensive-treatment group. Significantly fewer participants reached a serum creatinine level of 2 mg/dL or greater in the intensive-treatment vs the conventional-treatment group (5 vs 19, P =.004), but there were no differences in mean log clearance values. Although small numbers of patients required dialysis and/or transplantation, fewer patients experienced either of these outcomes in the intensive group (4 vs 7, P =.36). CONCLUSIONS: The persistent beneficial effects on albumin excretion and the reduced incidence of hypertension 7 to 8 years after the end of the DCCT suggest that previous intensive treatment of diabetes with near-normal glycemia during the DCCT has an extended benefit in delaying progression of diabetic nephropathy.

Adolescent↗