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Effect of glycemic control on growth velocity in children with IDDM.

OBJECTIVE: To determine the effect of glycemic control on growth velocity in children with insulin-dependent diabetes mellitus. RESEARCH DESIGN AND METHODS: One hundred twenty-two children with insulin-dependent diabetes mellitus were studied over a 5-yr period. Every 4 mo, glycemic control was assessed by measuring total glycosylated hemoglobin (GHb), pubertal status was determined by physical examination, and height was measured with a stadiometer. Height measurements were normalized for age and sex by converting them to tau scores (the number of SD above or below the mean for age and sex). Alterations in growth velocity were determined by the change in tau scores (delta tau) between visits (i.e., no change in tau score = normal growth velocity; decrease in tau score = growth deceleration; and increase in tau score = growth acceleration). RESULTS: A linear relationship was seen between GHb levels and the change in tau scores (r = -0.117, P = 0.001). GHb values less than 8% were associated with growth acceleration (delta tau = +0.10 +/- 0.03), and the greatest growth deceleration occurred when GHb was greater than 16% (delta tau = -0.07 +/- 0.03). The level of GHb at which growth suppression occurred (mean delta tau became negative) was dependent on pubertal status: Tanner stage 1 greater than or equal to 10%, Tanner stages 2 and 3 greater than or equal to 8%, Tanner stages 4 and 5 greater than or equal to 16%. CONCLUSIONS: Linear growth velocity in children with insulin-dependent diabetes mellitus is heavily related to metabolic control. Children who are prepubertal or in the early stages of puberty are the most vulnerable to growth suppression. Once puberty is well established, growth suppression does not occur until marked hyperglycemia (GHb greater than 16%) exists.

Adolescent↗

Cotherapy with recombinant human insulin-like growth factor I and insulin improves glycemic control in type 1 diabetes. RhIGF-I in IDDM Study Group.

OBJECTIVE: To study the effects of 12 weeks of cotherapy with recombinant human IGF-I (rhIGF-I) and insulin on glycemic control in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: The study population consisted of 223 patients who ranged in age from 11-66 years and were randomized in a double-blind study to receive 12 weeks of treatment with twice-daily subcutaneous injections of placebo (n = 54), or rhIGF-I at a dose (A.M/P.M) of 40/40 micrograms/kg (n = 56), 80/40 micrograms/kg (n = 57), or 80/60 micrograms/kg (n = 56), while continuing to receive standard insulin therapy. Patients were instructed to test blood glucose levels four times daily and adjust insulin doses to optimize blood glucose control. HbAlc, insulin requirements, body weight, and parameters of the IGF-IGF-binding protein axis were assessed before and during treatment. RESULTS: All groups were comparable at baseline with respect to mean age, gender distribution, duration of diabetes, HbAlc, and BMI. Cotherapy with rhIGF-I/insulin produced a mean decrease in HbAlc of 1.2%, compared with a 0.7% decrease in HbAlc for patients receiving intensified insulin therapy alone (P < or = 0.01). Subjects receiving rhIGF-I/insulin cotherapy also decreased their daily insulin usage by 11-19%, compared with a 7% increase in insulin usage reported by the placebo group. Moreover, the incidence of hypoglycemia was similar in subjects treated with rhIGF-I/Insulin cotherapy compared with those treated with insulin alone, despite the better glycemic control of the former group. The 40/40 dose of rhIGF-I was well tolerated. Higher doses of rhIGF-I did not further improve efficacy yet were associated with unacceptable levels of adverse events, including edema, jaw pain, and early worsening of retinopathy. CONCLUSIONS: These results demonstrate that rhIGF/insulin cotherapy improves glycemic control in patients with type 1 diabetes better than optimized insulin management alone; longer-term trials would be required to determine an acceptable benefit-risk profile.

Adult↗

Effects of quality improvement strategies for type 2 diabetes on glycemic control: a meta-regression analysis.

CONTEXT: There have been numerous reports of interventions designed to improve the care of patients with diabetes, but the effectiveness of such interventions is unclear. OBJECTIVE: To assess the impact on glycemic control of 11 distinct strategies for quality improvement (QI) in adults with type 2 diabetes. DATA SOURCES AND STUDY SELECTION: MEDLINE (1966-April 2006) and the Cochrane Collaboration's Effective Practice and Organisation of Care Group database, which covers multiple bibliographic databases. Eligible studies included randomized or quasi-randomized controlled trials and controlled before-after studies that evaluated a QI intervention targeting some aspect of clinician behavior or organizational change and reported changes in glycosylated hemoglobin (HbA1c) values. DATA EXTRACTION: Postintervention difference in HbA1c values were estimated using a meta-regression model that included baseline glycemic control and other key intervention and study features as predictors. DATA SYNTHESIS: Fifty randomized controlled trials, 3 quasi-randomized trials, and 13 controlled before-after trials met all inclusion criteria. Across these 66 trials, interventions reduced HbA(1c) values by a mean of 0.42% (95% confidence interval [CI], 0.29%-0.54%) over a median of 13 months of follow-up. Trials with fewer patients than the median for all included trials reported significantly greater effects than did larger trials (0.61% vs 0.27%, P = .004), strongly suggesting publication bias. Trials with mean baseline HbA1c values of 8.0% or greater also reported significantly larger effects (0.54% vs 0.20%, P = .005). Adjusting for these effects, 2 of the 11 categories of QI strategies were associated with reductions in HbA(1c) values of at least 0.50%: team changes (0.67%; 95% CI, 0.43%-0.91%; n = 26 trials) and case management (0.52%; 95% CI, 0.31%-0.73%; n = 26 trials); these also represented the only 2 strategies conferring significant incremental reductions in HbA1c values. Interventions involving team changes reduced values by 0.33% more (95% CI, 0.12%-0.54%; P = .004) than those without this strategy, and those involving case management reduced values by 0.22% more (95% CI, 0.00%-0.44%; P = .04) than those without case management. Interventions in which nurse or pharmacist case managers could make medication adjustments without awaiting physician authorization reduced values by 0.80% (95% CI, 0.51%-1.10%), vs only 0.32% (95% CI, 0.14%-0.49%) for all other interventions (P = .002). CONCLUSIONS: Most QI strategies produced small to modest improvements in glycemic control. Team changes and case management showed more robust improvements, especially for interventions in which case managers could adjust medications without awaiting physician approval. Estimates of the effectiveness of other specific QI strategies may have been limited by difficulty in classifying complex interventions, insufficient numbers of studies, and publication bias.

Blood Glucose↗

Self-care behaviors in insulin-dependent diabetes: evaluative tools and their associations with glycemic control.

Clarified the relationships between self-care behaviors and illness-specific outcomes in approximately 270 youths with IDDM. Youths were assessed at three points in time using a semistructured interview measure and multiple indices of dietary intake and physical activity with two different methodologies (i.e., recalls, logs). Glycemic control was most strongly related to the semistructured Self-Care Adherence Interview (SCAI); and second to the overall quality of the youth's dietary intake. The SCAI also predicted glycemic control over time. Physical activity levels and specific nutritional components from the logs and recalls were generally unrelated to glycemic control.

Adolescent↗

Serum protein-bound hexose in diabetes: the effect of glycemic control.

To determine whether the carbohydrate content of serum proteins is related to overall glycemic control, we studied serum protein-bound hexose and glycosylated hemoglobin [HbA1(a+b+c)] in 37 ambulant diabetic patients and 32 nondiabetic controls. Protein-bound hexose was correlated with HbA1(a+b+c) in the diabetic patients (r = 0.36, P less than 0.025). The mean protein-bound hexose level of the diabetic patients was greater than that of the controls (190.8 versus 174.7 mg/dl, P less than 0.01), but diabetic patients with HbA1(a+b+c) less than 12% had a mean protein-bound hexose similar to the controls. In nine of the diabetic patients, mean protein-bound hexose and HbA1(a+b+c) were significantly reduced during a period of intensive outpatient care, while two major serum glycoproteins, haptoglobins and alpha-1-antitrypsin, were unchanged. Our findings support the hypothesis that increased glycosylation of serum proteins may occur in diabetes mellitus; this abnormality in serum protein-bound hexose may be corrected by close attention to overall glycemic control.

Blood Proteins↗

Glycemic control and treatment failure with pioglitazone versus glibenclamide in type 2 diabetes mellitus: a 42-month, open-label, observational, primary care study.

BACKGROUND: Insulin resistance and declining beta-cell function are the core defects in type 2 diabetes mellitus. It has been suggested that deteriorating glycemic control is related to baseline hemoglobin A(1c) (HbA(1c)) values and remaining beta-cell function. PATIENTS AND METHODS: We report glycemic data from a 3.5-year, open-label, observational, primary care study comparing 30 mg/day pioglitazone with 3.5 mg/day glibenclamide add-on to stable metformin monotherapy in 500 patients with type 2 diabetes. Insulin commencement was considered for patients with HbA(1c) > or = 8.0% or when vascular complications occurred. The change in HbA(1c) compared with baseline and the difference in time to failure to maintain glycemic control were calculated. RESULTS: At endpoint, HbA(1c) had decreased by 1.0% in the pioglitazone group (p < 0.005) and by 0.6% in the glibenclamide group (p < 0.05). Annual progression rates to insulin treatment were 6.6% (pioglitazone) and 16.4% (glibenclamide; p < 0.001 between-group difference). Mean weight increases of 3.5 +/- 0.42 kg in the pioglitazone group and 3.3 +/- 0.38 kg in the glibenclamide group were noted. Overall, both treatments were well tolerated. CONCLUSIONS: Pioglitazone add-on to metformin revealed significant benefits in long-term glycemic control compared with glibenclamide. This difference may be explained by a large between-group difference in HOMA-S, which was shown to correlate significantly to the change in HbA(1c). This suggests that a strategy to reduce insulin resistance to lower the burden of the beta-cell is superior to treatment with glibenclamide.

Aged↗

Home testing of fructosamine improves glycemic control in patients with diabetes.

OBJECTIVE: To determine whether weekly fructosamine testing at home by patients with type 2 diabetes, combined with therapeutic intervention when necessary on the basis of the results, would lead to improved glycemic control in comparison with usual care during a 3-month period. METHODS: In a prospective study, 25 patients with glycosylated hemoglobin (HbA1c) values above 8.0% were randomized into 2 groups. Both groups, a glucose-only testing group (14 patients with an initial mean HbA1c of 9.4 +/- 0.9%) and a combined glucose plus fructosamine testing group (11 patients with an initial mean HbA1c of 9.2 +/- 0.7%), received therapeutic intervention at the time of randomization. Both groups were instructed to perform blood glucose testing up to four times per day. The combined glucose plus fructosamine testing group was also instructed to perform weekly fructosamine testing in addition to the glucose testing and to telephone the investigator if their home-testing fructosamine value exceeded 350 mmol/L (approximately equivalent to HbA1c of 7.8%), whereupon the investigator implemented further interventions. Both groups returned in 3 months, at which time HbA1c testing was repeated in order to determine whether glycemic control had changed. RESULTS: The study results after 3 months showed that the HbA1c values in the combined glucose plus fructosamine testing group decreased from 9.2 +/- 0.7% to 8.0 +/- 0.5% (P<0.0001). In contrast, the HbA1c values in the glucose-only testing group declined from 9.4 +/- 0.9% to 9.1 +/- 1.3%, a difference that was not significant. CONCLUSION: In the 3 months after a change in therapy for type 2 diabetes, weekly home testing of fructosamine, combined with therapeutic interventions based on the results, led to a more rapid and significant improvement in glycemic control than did the usual regimen of glucose-only testing.

Blood Glucose Self-Monitoring↗

Self-care behaviors and glycemic control in type I diabetes.

This study investigated the degree of adherence to different aspects of the diabetic treatment regimen (insulin injections, glucose testing, diet, and exercise), the consistency of adherence across different regimen areas, and relationships between adherence and glycemic control. A predominantly adult community sample of 93 insulin dependent outpatients participated in the prospective study that involved two series of home interviews separated by a 6-month interval. Multiple measures of adherence (e.g. self-report, interview/recall, self-monitoring, and objective indices) were collected for each regimen area. Results indicated that the degree of adherence was higher for medication taking and glucose testing than for regimen tasks requiring greater lifestyle modifications such as diet and exercise; there were few strong relationships between subjects' adherence to one area of the regimen and the extent to which they adhered to other regimen tasks; and no clear relationship between adherence and glycemic control could be demonstrated through either bivariate or multivariate analyses. It is recommended that regimen adherence be considered in the context of other factors that may influence glycemic control (e.g. stress, individual metabolic factors, appropriateness of regimen prescriptions) rather than assuming a one-to-one relationship between adherence and control.

Adolescent↗

Early glycemic control, age at onset, and development of microvascular complications in childhood-onset type 1 diabetes: a population-based study in northern Sweden.

OBJECTIVE: The aim of this work was to study the impact of glycemic control (HbA(1c)) early in disease and age at onset on the occurrence of incipient diabetic nephropathy (MA) and background retinopathy (RP) in childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: All children, diagnosed at 0-14 years in a geographically defined area in northern Sweden between 1981 and 1992, were identified using the Swedish Childhood Diabetes Registry. From 1981, a nationwide childhood diabetes care program was implemented recommending intensified insulin treatment. HbA(1c) and urinary albumin excretion were analyzed, and fundus photography was performed regularly. Retrospective data on all 94 patients were retrieved from medical records and laboratory reports. RESULTS: During the follow-up period, with a mean duration of 12 +/- 4 years (range 5-19), 17 patients (18%) developed MA, 45 patients (48%) developed RP, and 52% had either or both complications. A Cox proportional hazard regression, modeling duration to occurrence of MA or RP, showed that glycemic control (reflected by mean HbA(1c)) during the follow-up was significantly associated with both MA and RP when adjusted for sex, birth weight, age at onset, and tobacco use as potential confounders. Mean HbA(1c) during the first 5 years of diabetes was a near-significant determinant for development of MA (hazard ratio 1.41, P = 0.083) and a significant determinant of RP (1.32, P = 0.036). The age at onset of diabetes significantly influenced the risk of developing RP (1.11, P = 0.021). Thus, in a Kaplan-Meier analysis, onset of diabetes before the age of 5 years, compared with the age-groups 5-11 and >11 years, showed a longer time to occurrence of RP (P = 0.015), but no clear tendency was seen for MA, perhaps due to lower statistical power. CONCLUSIONS: Despite modern insulin treatment, >50% of patients with childhood-onset type 1 diabetes developed detectable diabetes complications after approximately 12 years of diabetes. Inadequate glycemic control, also during the first 5 years of diabetes, seems to accelerate time to occurrence, whereas a young age at onset of diabetes seems to prolong the time to development of microvascular complications.

Adolescent↗

Benefits of micronised Fenofibrate in type 2 diabetes mellitus subjects with good glycemic control.

AIMS: To determine the effects of micronised fenofibrate on lipids and low density lipoprotein (LDL) subfraction in well-controlled diabetic subjects with mild elevations in cholesterol levels. METHODS: Thirty-five male type 2 diabetic subjects with LDL(3) greater than 100 mg/dl and good glycemic control (mean HbA1c 6.7%) were treated with micronised fenofibrate in an open labeled study for 6 months. Anthropometric indices, blood pressure, lipids, glucose, insulin, apolipoprotein A-I and B, and LDL subfraction by density ultracentrifugation were obtained after an overnight fast of 10 h, at the beginning and end of the 6 months treatment period. RESULTS: The blood pressure, waist to hip ratio, body mass index and glycemic control remained unchanged throughout the 6 months study period. Mean serum triglyceride fell from 2.49 to 1.72 mmol/l (33%) whilst HDL cholesterol increased from 0.88 to 0.96 mmol/l (10.8%). There were no significant changes in total or LDL cholesterol. Both LDL(1) and LDL(2) rose significantly whilst the dense LDL(3) fell from a mean of 148 to 85 mg/dl (43% reduction). Fenofibrate changed the LDL subfraction distribution from dense LDL(3) particles towards buoyant LDL(1) and LDL(2) particles in 63% of the subjects. No subjects had elevations in transaminases greater than three-fold or creatine kinase greater than ten-fold from pre-treatment levels. CONCLUSION: Diabetic subjects with mild hypercholesterolemia and good glycemic control may benefit from therapy with micronised fenofibrate because of the reduction in serum triglyceride, elevation in HDL cholesterol and a shift in LDL subfraction towards a non-atherogenic form.

Adult↗

Effect of reinstitution of good glycemic control on retinal oxidative stress and nitrative stress in diabetic rats.

Clinical and experimental studies have shown that reinstitution of good glycemic control (GC) after a period of poor glycemic control (PC) does not produce immediate benefits on the progression of retinopathy, and hyperglycemia is sufficient to initiate the development of diabetic retinopathy. In this study, the effect of reinstitution of GC on hyperglycemia-induced increased oxidative stress and nitrative stress was evaluated in the retina of rats maintained in PC before initiation of GC. In diabetic rats, 2 or 6 months of PC (GHb >11.0%) was followed by 7 months of GC (GHb <5.5%). Reinstitution of GC after 2 months of PC inhibited elevations in retinal lipid peroxides and NO levels by approximately 50%, but failed to have any beneficial effects on nitrotyrosine formation. However, reversal of hyperglycemia after 6 months of PC had no significant effect on retinal oxidative stress and NO levels (P < 0.02 vs. normal). In the same rats, inducible nitric oxide synthase expression and nitrotyrosine levels remained elevated by >80% compared with normal rats or rats kept in GC for the duration. This suggests that oxidative and nitrative modifications in retina occur early in the course of development of retinopathy in diabetes. These abnormalities are not easily reversed by reinstitution of GC, and the duration of PC before initiation of GC influences the outcome of the reversal. Characterization of the abnormalities responsible for the resistance of retinopathy to arrest after reinstitution of GC will help identify potential future therapies to inhibit progression of diabetic retinopathy.

Animals↗

Relationship of skin thickness to duration of diabetes, glycemic control, and diabetic complications in male IDDM patients.

Skin thickness is primarily determined by collagen content and is increased in insulin-dependent diabetes mellitus (IDDM). We measured skin thickness in 66 IDDM patients aged 24-38 yr and investigated whether it correlated with long-term glycemic control and the presence of certain diabetic complications. With univariate analysis, skin thickness was increased and significantly related to duration of diabetes (P less than .001), previous glycemic control (P less than .001), retinopathy (P less than .001), cheiroarthropathy (P less than .001), and vibration-perception threshold (P less than .05). There was a negative correlation between forced expiratory volume at 1 s (P less than .05) and vital capacity (P less than .05) with duration of diabetes. Neither skin thickness nor ankle arteriomedial wall calcification correlated with abnormal autonomic function tests. When corrected for duration of diabetes, there was a weak correlation between skin thickness and glycemic control (P less than .05) but no correlation with retinopathy, cheiroarthropathy, and vibration-perception threshold. This study confirms that there are widespread connective tissue changes in diabetes mellitus, although the biochemistry needs further elucidation.

Adult↗

Glycemic control is related to the electrophysiologic severity of diabetic peripheral sensorimotor polyneuropathy.

OBJECTIVE: The aim of the present study was to examine risk factors for the electrophysiologic severity of diabetic peripheral sensorimotor polyneuropathy (DSP). RESEARCH DESIGN AND METHODS: A total of 97 patients with type 1 diabetes (25 patients) or type 2 diabetes (72 patients) were included in this cross-sectional study. Nerve conduction studies (NCS) were performed on median motor and sensory nerves, peroneal motor nerve, and both sural nerves. The severity of DSP was expressed as the sum of nerve conduction velocities (SNCV) and the score of distal amplitudes (SAMP) of the above-mentioned nerves. General linear models were used to assess the relationship between overall severity of DSP as well as the severity of lower extremity, upper extremity, motor nerve, or sensory nerve involvement and various risk factors. RESULTS: GHb was significantly related to both SNCV and SAMP in univariate and multivariate regression analyses. This relationship was present in models where GHb was handled either as a continuous variable or as a categorical variable with highest significance level, with a GHb cutoff level of 9%. The difference in NCV for individual nerves in patients with good-to-moderate glycemic control (GHb < or =9%) and those with poor glycemic control (GHb > or =9%) ranged from 1.8 to 3.6 m/s. SAMP was also significantly lower in patients with poor control. SNCV was also significantly related in multivariate analysis to duration of diabetes and height, while SAMP was related to duration of diabetes, age, and male sex. CONCLUSIONS: The severity of DSP expressed by electrophysiologic criteria was significantly related to glycemic control in a study including patients with type 1 or type 2 diabetes. Based on the results of the present study, it might be predicted that better diabetic control would decrease the severity of DSP.

Aldehyde Reductase↗

Serum fructosamine (alkaline-reducing activity) for evaluation of glycemic control in diabetic patients.

The values of serum fructosamine were significantly higher in 75 diabetic patients than those of metabolically healthy controls. Significant correlation could be observed between the glycated hemoglobin and serum fructosamine values in diabetics. Furthermore, significant correlations were established between the serum fructosamine values and the mean blood glucose as well as the mean 24 hours urinary glucose values measured 10-14 days previously in diabetics. Glycated hemoglobin values should be measured in diabetics for long-term assessment of glycemic control while serum fructosamine values could be useful in clinical practice for assessment of overall glycemic control of the previous two weeks in diabetic patients. Not only long-term glycemic control but medium-term alterations in blood glucose concentrations could be evaluated by simultaneous measurements of glycated hemoglobin and serum fructosamine values in diabetics.

Adult↗

Symptoms and well-being in relation to glycemic control in type II diabetes.

OBJECTIVE: To describe the cross-sectional relation between glycemic control and physical symptoms, emotional well-being, and general well-being in patients with type II diabetes. RESEARCH DESIGN AND METHODS: The study population consisted of 188 patients with type II diabetes between 40 and 75 years of age. Patients were treated with blood glucose-lowering agents or had either a fasting venous plasma glucose level > or = 7.8 mmol/l or an HbA1c level > 6.1%. Multiple regression analyses were performed. Dependent variables were scores on the Type II Diabetes Symptom Checklist, the Profile of Mood States, the Affect Balance Scale, and questions regarding general well-being. The primary determinant under study was HbA1c. In addition, age, sex, neuroticism (indicating a general tendency to complain), insulin use, and comorbidity were included as determinants in all analyses. Other potential determinants taken into consideration were hypoglycemic complaints, marital status, diabetes duration, cardiovascular history, blood pressure, BMI, waist-to-hip ratio, perceived burden of treatment, and smoking. None of these potential determinants had to be included to correct confounding of the relation between HbA1c and well-being scores. RESULTS: Higher HbA1c levels were significantly associated with higher symptom scores (total score, hyperglycemic score, and neuropathic score), with worse mood (total score, displeasure score, depression, tension, fatigue), and with worse general well-being. The relative risks varied between 1.02 and 1.36 for each percentage difference in HbA1c. The relation between HbA1c and some mood states was modified by neuroticism: in the less neurotic patient (i.e., one who is less inclined to complain), the relation was more evident. CONCLUSIONS: These data suggest that better glycemic control in type II diabetes is associated with fewer physical symptoms, better mood, and better well-being, in a nonhypoglycemic HbA1c range.

Adult↗

Improved glycemic control by acarbose therapy in hypertensive diabetic patients: effects on blood pressure and hormonal parameters.

A double-blind, randomized, placebo-controlled study was carried out on 44 hypertensive type 2 diabetic subjects previously treated by diet associated or not with sulfonylurea to assess the effects of acarbose-induced glycemic control on blood pressure (BP) and hormonal parameters. Before randomization and after a 22-week treatment period (100 to 300 mg/day), the subjects were submitted to a standard meal test and to 24-h ambulatory BP monitoring (ABPM) and had plasma glucose, glycosylated hemoglobin, lipid profile, insulin, proinsulin and leptin levels determined. Weight loss was found only in the acarbose-treated group (75.1 +/- 11.6 to 73.1 +/- 11.6 kg, P<0.01). Glycosylated hemoglobin decreased only in the acarbose group (6.4 +/- 1.7 to 5.6 +/- 1.9%, P<0.05). Fasting proinsulin decreased only in the acarbose group (23.4 +/- 19.3 to 14.3 +/- 13.6 pmol/l, P<0.05), while leptin decreased in both (placebo group: 26.3 +/- 6.1 to 23.3 +/- 9.4 and acarbose group: 25.0 +/- 5.5 to 22.7 +/- 7.9 ng/ml, P<0.05). When the subset of acarbose-treated patients who improved glycemic control was considered, significant reductions in diurnal systolic, diastolic and mean BP (102.3 +/- 6.0 to 99.0 +/- 6.6 mmHg, P<0.05) were found. Acarbose monotherapy or combined with sulfonylurea was effective in improving glycemic control in hypertensive diabetic patients. Acarbose-induced improvement in metabolic control may reduce BP in these patients. Our data did not suggest a direct action of acarbose on insulin resistance or leptin levels.

Acarbose↗

Closed-loop glycemic control with a wearable artificial endocrine pancreas. Variations in daily insulin requirements to glycemic response.

We succeeded in miniaturizing a needle-type glucose monitoring system with characteristics suitable for application in a wearable, closed-loop control system. A wearable artificial endocrine pancreas (12 X 15 X 6 cm, 400 g) consisting of a sensor, a microcomputer system that calculates insulin and glucagon infusion rates, and two roller pumps was developed. Continuous glucose monitoring by a glucose sensor inserted in the subcutaneous tissue of the forearm or abdomen of healthy and diabetic volunteers revealed that glucose concentrations in subcutaneous tissue were 10% lower than, but were highly correlated with, blood glucose concentrations in the range of 49-388 mg/dl. Glycemic control was established in diabetic patients by intravenously infusing insulin in response to measured glucose concentrations on a moment-to-moment basis for a period of several days. By comparing the glycemic control obtained in each patient treated with multiple insulin injections or open-loop subcutaneous insulin infusion, the superiority of feedback control with the system was clearly demonstrated. During continuous glycemic regulation, day-to-day variations of insulin requirements were recognized in both basal insulin infusion and postprandial insulin infusion rates in response to identical meals and exercise. These data suggest the feasibility of long-term glycemic control in diabetic subjects with a wearable artificial endocrine pancreas, and indicate that to overcome changes in individual metabolic characteristics on a moment-to-moment basis, a closed-loop glycemic control system may be essential for ambulatory diabetic patients.

Adult↗

Inactive aldehyde dehydrogenase 2 worsens glycemic control in patients with type 2 diabetes mellitus who drink low to moderate amounts of alcohol.

BACKGROUND: Alcohol intake can have hypoglycemic or hyperglycemic effects in patients with type 2 diabetes mellitus. The present study was designed to investigate the glycemic control of male patients with diabetes mellitus from the aspect of the genetic status of alcohol metabolism. METHODS: One hundred sixty-three men with type 2 diabetes mellitus were enrolled in the present study. They were all outpatients at the Diabetes Center of Saiseikai Central Hospital. The genotype of the aldehyde dehydrogenase 2 (ALDH2) gene of each patient was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the patients were divided into those with active or inactive ALDH2 phenotype. We compared the amount of habitual alcohol intake and clinical data that included physical findings and blood chemistry of the patients in the active and inactive ALDH2 groups. The glycemic control of each patient was evaluated by the serum level of HbAlc. RESULTS: Of the 163 patients with type 2 diabetes mellitus, 90 patients had the active ALDH2 phenotype and 73 patients had the inactive ALDH2 phenotype. The mean HbA1c level of the active ALDH2 group was nearly the same as that of the inactive ALDH2 group. However, the HbA1c level of the light-to-moderate drinkers (1-400 g/week) in the inactive ALDH2 group was highest and was significantly higher than the HbA1c level of the light-to-moderate drinkers of the active ALDH2 group. The HbA1c of the patients with diabetic complications was higher than the HbAlc of those without diabetic complications in both the active and inactive ALDH2 groups. However, the HbA1c level of the light-to-moderate drinkers without diabetic complications in the inactive ALDH2 group was significantly higher and the incidence of 24 hr urinary C-peptide was higher than the respective level of the light-to-moderate drinkers without diabetic complications in the active ALDH2 group. CONCLUSIONS: Habitual light-to-moderate alcohol intake worsens glycemic control in diabetic patients who have the inactive ALDH2 phenotype. The data on 24 hr urinary C-peptide level suggested that increased acetaldehyde after light-to-moderate drinking by inactive ALDH2 diabetic patients may increase the HbA1c value by the insulin-resistant condition that resulted in hyperinsulinemia.

Adult↗