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PubMedDate not supplied

Effect of glycemic control on the growth velocity and several metabolic parameters of conventionally treated children with insulin dependent diabetes mellitus.

To determine the effect of glycemic control on the growth velocity and several metabolic parameters of children with insulin-dependent diabetes mellitus (IDDM), 79 patients with IDDM, 45 females and 34 males with a mean chronological age of 8.4 +/- 3.0 years were followed over a 5-year period starting at the onset of diabetes. Glycemic control was assessed by measuring total glycosylated hemoglobin; children were divided into better controlled, GHb < 9%, 30 children (Group A) and worse controlled, GHb > or = 9%, 49 patients (Group B). Growth velocity was significantly lower, in the five years of follow up, in the worse controlled patients when compared to the better controlled subjects (4.8 +/- 1.6 vs 6.7 +/- 2.2 cm/yr after the first year and 5.0 +/- 2.0 vs 6.5 +/- 1.8 cm/yr after the fifth year, in group B and group A, respectively). Higher cholesterol (185.3 +/- 33.7 vs 158.8 +/- 39.5 mg/dl) and triglyceride levels (85.9 +/- 43.5 vs 71.0 +/- 37.4 mg/dl) were apparent in the worse controlled patients, when compared to the better controlled children. Insulin dose was not significantly different in the two groups (0.76 +/- 0.3 vs 0.84 +/- 0.4 U/kg/day in the 1st year and 0.9 +/- 0.3 vs 0.92 +/- 0.4 U/kg/day in the 5th year, in group B and A respectively). Although both groups received the same initial and long term training by our pediatric diabetes team, more frequent blood glucose monitoring, better record keeping and rotation of injection sites and more clinic visits were clearly noted in the better controlled group. Ketoacidotic episodes were more common in the worse controlled patients, while better controlled children had a higher number of hypoglycemic episodes. In conclusion, we have found poor glycemic control, as reflected by higher glycosylated hemoglobin levels, to affect the growth velocity and several metabolic parameters of children with diabetes followed for a five-year period. Other factors besides insulin dose and initial and subsequent diabetic education seem to play a role in their glycemic control.

Blood Glucose↗

PubMed1999

Improved postprandial glycemic control during treatment with Humalog Mix25, a novel protamine-based insulin lispro formulation. Humalog Mix25 Study Group.

OBJECTIVE: Humalog Mix25 is a manufactured premixed insulin formulation containing insulin lispro and a novel insulin lispro-protamine formulation (NPL) in a ratio of 25:75%. The objective of this study was to compare Humalog Mix25 to human insulin 30/70 (30% regular insulin/70% NPH) with respect to glycemic control. RESEARCH DESIGN AND METHODS: Humalog Mix25 was compared with human insulin 30/70 in 89 individuals with type 2 diabetes during a 6-month randomized open-label two-period crossover study. Each insulin was administered twice daily, before the morning and evening meals. Information regarding self-monitored blood glucose (BG), hypoglycemic episodes (hypoglycemic signs or symptoms or BG < or = 3.0 mmol/l), insulin dose, and HbA1c was collected. RESULTS: Treatment with Humalog Mix25 resulted in better postprandial glycemic control after the morning and evening meals compared with treatment with human insulin 30/70. Overall glycemic control and the incidence of hypoglycemia were comparable between the treatments. CONCLUSIONS: In comparison to treatment with human insulin 30/70, twice daily administration of Humalog Mix25 resulted in improved postprandial glycemic control, similar overall glycemic control, and the convenience of dosing immediately before meals.

Blood Glucose↗

PubMedDate not supplied

Family environment and glycemic control: a four-year prospective study of children and adolescents with insulin-dependent diabetes mellitus.

An onset cohort of children and adolescents with insulin-dependent diabetes mellitus (IDDM) and their parents were studied. Aspects of family environment were evaluated at study inception, and their influence on the initial level of, and change in, glycemic control over 4 years was examined. Family measures of expressiveness, cohesiveness, and conflict were linked to differences in the longitudinal pattern of glycemic control. In particular, the encouragement to act openly and express feelings directly (expressiveness) seemed to ameliorate deterioration of glycemic control over time in both boys and girls. Boys were especially sensitive to variations in family cohesiveness and conflict; those from more cohesive and less conflicted families showed less deterioration in glycemic control. This study demonstrated the important influence of family psychosocial factors present at diabetes onset on glycemic control in children and adolescents over the first 4 years of IDDM.

Adaptation, Psychological↗

PubMed1992

Does glycemic control of type II diabetes suffice to control diabetic dyslipidemia? A community perspective.

OBJECTIVE: To assess the extent to which glycemic control by itself results in satisfactory control of diabetic dyslipidemia. RESEARCH DESIGN AND METHODS: A population-based case series consisting of 386 Mexican Americans and 94 non-Hispanic whites with non-insulin-dependent (type II) diabetes was studied. All subjects answered questions about their medical history and care received and underwent a standardized oral glucose tolerance test and measurements of fasting serum lipid and lipoprotein concentrations. Three definitions of dyslipidemia were used: total cholesterol greater than 6.20 mM (240 mg/dl), triglyceride greater than 2.82 mM (250 mg/dl), and high-density lipoprotein cholesterol less than 0.90 mM (35 mg/dl). RESULTS: Despite having removed subjects receiving lipid-lowering drugs, diabetic subjects who had been previously diagnosed and were under medical care exhibited a lower prevalence of hypertriglyceridemia than those who were newly diagnosed at the time of their survey visit, suggesting that conventional management was associated with a reduced frequency of this dyslipidemia. Among previously diagnosed cases, the prevalence of dyslipidemia rose with worsening glycemic control but there was little association with type of therapy (diet only, oral agents, or insulin) or frequency of physician visits. In general, the prevalence of dyslipidemia in diabetic subjects remained higher than in nondiabetic subjects, despite hypoglycemic therapy. CONCLUSIONS: The results suggest that glycemic control by itself does not suffice to control diabetic dyslipidemia and that significant numbers of diabetic subjects will need direct lipid management. Clinical trials are urgently needed to define the optimum management strategy for diabetic dyslipidemia.

Adult↗

PubMedDate not supplied

Psychosocial correlates of glycemic control: the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study.

The psychosocial correlates of glycemic control were examined in an incident cohort of childhood onset insulin-dependent diabetic subjects aged 18 years or older (n = 592). Glycosylated hemoglobin was measured at subjects' clinical examination, and questionnaires on diabetes self-care activity, barriers to regimen adherence and social support were completed. Demographic information was also collected. Glycosylated hemoglobin (GHb) was correlated with age, income and educational attainment (correlations coefficients between -0.1 and -0.2; P < 0.01), suggesting that older, more educated and wealthier patients have better glycemic control. GHb was also inversely associated with the degree of self-care activity (r = -0.11; P < 0.01), in particular administering injections at the recommended times and the frequency of performing blood/urine tests. Factors related to self-care behavior were identified, and included degree of social support (r = 0.14; P < 0.001) and patients' reports of difficulties adhering to their self-care regimen (r = -0.3; P < 0.0001). Gender was also related to self-care activities, with women reporting more self-care behavior than men (mean self-care scores 17.9 +/- 3.7 vs. 16.9 +/- 4.0; P < 0.01). Thus psychosocial factors (e.g. low income and education) may have an important effect on glycemic control in adults, and also (e.g. social support and adherence difficulties) seem particularly important in influencing the performance of self-care. As good metabolic control may help avoid the progression of diabetic complications, efforts need to be directed towards patients with these characteristics who are more likely to experience difficulties with self-care.

Adolescent↗

PubMed1998

Relation of glycemic control to diabetic complications and health outcomes.

Data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) demonstrated that the incidence of diabetic complications is directly related to glycemic control. The results of the Diabetes Control and Complications Trial and Stockholm Study showed that intensive insulin therapy and improved glycemic control reduced diabetic complications in people with type 1 diabetes. Results of the U.K. Prospective Diabetes Study Group and the Kumamoto trial also support the relationship between glycemic control and diabetic complications in individuals with type 2 diabetes. Preliminary WESDR health outcomes data suggest that higher levels of glycemia are related to a decreasing quality of life. This study and others showing that higher levels of glycemia are associated with an increased incidence of complications suggest that it is the complications of diabetes that contribute to a decrease in quality of life. Despite evidence of the benefits of improved glycemic control, a large percentage of people with diabetes maintain poor glucose control in part because of the limitations of the therapies available for diabetes management.

Albuminuria↗

PubMed2001

Comorbidity and glycemic control in patients with type 2 diabetes.

BACKGROUND: It is commonly believed that good glycemic control is hard to achieve in patients with diabetes mellitus and concurrent chronic illnesses. OBJECTIVE: To determine the impact of comorbidity on glycemic control at presentation and subsequent follow-up in patients with type 2 diabetes. METHODS: We studied 654 consecutive patients who presented to a diabetes clinic in 1997. Comorbidity was rated using the Chronic Disease Score (CDS) index, which is a validated, weighted score that takes into account the patient's age, sex, and classes of medications. Univariate and multivariate linear regressions were used to determine the contribution of age, body mass index (calculated as weight in kilograms divided by the square of height in meters), diabetes duration, type of therapy, and CDS to initial hemoglobin A(1c) (HbA(1c)) level. A similar analysis was performed for the 169 patients with follow-up HbA(1c) levels 6 months after presentation. RESULTS: Patients were 90% African American, and 66% female, with average age of 53 years. Average diabetes duration was 5 years; body mass index, 33; HbA(1c) level, 8.8%; and CDS, 1121 (range, 232-7953). At presentation, patients with higher CDSs tended to be older and to have a lower HbA(1c) level, but multivariate linear regression showed that receiving pharmacological therapy, younger age, and having a lower C-peptide level were the only significant contributors to HbA(1c) level. In the 169 follow-up patients, presenting characteristics were not significantly different from those of the full cohort: average initial HbA(1c) level was 8.8%; CDS, 1073. Their HbA(1c) level at 6 months averaged 7.5% and the CDS had no significant impact on their follow-up HbA(1c) level. CONCLUSION: Comorbidity does not appear to limit achievement of good glycemic control in patients with type 2 diabetes.

Age Distribution↗

PubMed2002

GI symptoms in diabetes mellitus are associated with both poor glycemic control and diabetic complications.

OBJECTIVE: Diabetes mellitus is associated with an increased prevalence of GI symptoms, but the mechanisms underlying symptoms are poorly defined and controversial. We aimed to determine whether there is a relationship between GI symptoms and both diabetic complications and glycemic control. METHODS: We performed a cross-sectional questionnaire study of 1101 subjects with diabetes mellitus recruited from outpatient clinics (n = 209) and the community (n = 892). Data on eight GI symptom groups, complications of diabetes (retinopathy, neuropathy, nephropathy), and self-reported glycemic control were obtained from a validated questionnaire. Glycated hemoglobin was measured in 463 of the subjects, The association between diabetic complications, glycemic control, and GI symptoms was assessed using logistic regression analysis, adjusted for demographic and clinical factors. RESULTS: Of the 1101 subjects, 57% reported at least one complication. Diabetic complications were independently associated with both symptom complexity (number of symptom groups reported) (adjusted odds ratio = 1.92 per symptom group [95% CI = 1.51-2.45]) and seven of the eight GI symptom groups. For all symptom groups, the association was explained by self-reported symptoms of peripheral neuropathy. Poor glycemic control measured by both self-report and Hb A1c was an independent risk factor for upper GI symptoms, whereas other potential risk indicators, including duration and type of diabetes, were not significant. CONCLUSIONS: GI symptoms in diabetes mellitus may be linked to diabetic complications, particularly peripheral neuropathy, and to poor glycemic control.

Adult↗

PubMedDate not supplied

Improved perioperative glycemic control by continuous insulin infusion under supervision of an endocrinologist does not increase costs in patients with diabetes.

OBJECTIVE: To evaluate whether glycemic control can be improved perioperatively by implementing an insulin infusion protocol for patients with diabetes undergoing coronary artery bypass graft (CABG) surgery, without creating an additional financial burden. We also evaluated impact of such a protocol on hospital length of stay (LOS) and development of deep sternal wound infections (DSWI). METHODS: We developed an insulin infusion glycemic control protocol (IGCP) under supervision and consultation of an endocrinologist. Outcomes of CABG surgery patients with diabetes receiving our IGCP (year 2000) were compared to those of a conventional group of patients with diabetes undergoing CABG prior to the use of the IGCP (year 1999). Cost analysis was performed on data from the hospital's cost accounting database, which included additional costs related to the IGCP. RESULTS: The IGCP group (n=107) showed significantly better glycemic control (mean blood glucose level 183.5 mg/dl +/- SD 53.2 mg/dL; P<0.0001) than the conventional group (n = 81; mean blood glucose level 241.67 mg/dL +/- 75.93 mg/dL). Overall hospital costs were not significantly affected by the intervention. The IGCP group showed a trend toward shorter LOS (IGCP 6.34 days; conventional group 6.58 days) and a reduced rate of DSWI (IGCP 4.63%; conventional group 4.94%). CONCLUSIONS: Glycemic control can be improved by implementation of IGCP with no significant additional health care costs. Endocrinologist involvement did not increase costs and improved glycemic management of CABG patients with diabetes.

Blood Glucose↗

PubMed2002

Cost-effectiveness of intensive glycemic control, intensified hypertension control, and serum cholesterol level reduction for type 2 diabetes.

CONTEXT: Several treatment interventions can reduce complications of type 2 diabetes, but their relative cost-effectiveness is not known. OBJECTIVE: To estimate the incremental cost-effectiveness of intensive glycemic control (relative to conventional control), intensified hypertension control, and reduction in serum cholesterol level for patients with type 2 diabetes. DESIGN, SETTING, AND PATIENTS: Cost-effectiveness analysis of a hypothetical cohort of individuals living in the United States, aged 25 years or older, who were newly diagnosed as having type 2 diabetes. The results of the United Kingdom Prospective Diabetes Study (UKPDS) and other studies were used to create a model of disease progression and treatment patterns. Costs were based on those used in community practices in the United States. INTERVENTIONS: Insulin or sulfonylurea therapy for intensive glycemic control; angiotensin-converting enzyme inhibitor or beta-blocker for intensified hypertension control; and pravastatin for reduction of serum cholesterol level. MAIN OUTCOME MEASURES: Cost per quality-adjusted life-year (QALY) gained. Costs (in 1997 US dollars) and QALYs were discounted at a 3% annual rate. RESULTS: The incremental cost-effectiveness ratio for intensive glycemic control is $41 384 per QALY; this ratio increased with age at diagnosis from $9614 per QALY for patients aged 25 to 34 years to $2.1 million for patients aged 85 to 94 years. For intensified hypertension control the cost-effectiveness ratio is -$1959 per QALY. The cost-effectiveness ratio for reduction in serum cholesterol level is $51 889 per QALY; this ratio varied by age at diagnosis and is lowest for patients diagnosed between the ages of 45 and 84 years. CONCLUSIONS: Intensified hypertension control reduces costs and improves health outcomes relative to moderate hypertension control. Intensive glycemic control and reduction in serum cholesterol level increase costs and improve health outcomes. The cost-effectiveness ratios for these 2 interventions are comparable with those of several other frequently adopted health care interventions.

Adrenergic beta-Antagonists↗

PubMed1985

Rationale for glycemic control.

Whether long-term glycemic control will prevent the chronic vascular complications of diabetes mellitus remains unknown. Microangiopathy and accelerated macroangiopathy are prevalent in both type I, or insulin-dependent diabetes mellitus, and type II, or non-insulin-dependent diabetes mellitus. Microangiopathy is predominantly responsible for the excessive morbidity and mortality in type I diabetic patients, whereas accelerated macroangiopathy directly relates to the excessive morbidity and mortality in type II diabetic patients. Institution of euglycemia for short periods will reverse preclinical, functional, renal, and retinal abnormalities, but will not reverse clinical nephropathy and retinopathy. Intensive insulin therapy, although it increases the risk of hypoglycemic encephalopathy, seems rational for type I diabetic patients without vascular complications who can recognize and respond normally to hypoglycemia. In patients with type II diabetes, sulfonylurea therapy, which is associated with fewer adverse reactions than intensive insulin therapy, may lower the risk of atherosclerosis development by correcting hyperglycemia and associated lipid abnormalities.

Basement Membrane↗

PubMedDate not supplied

Improved glycemic control with use of continuous subcutaneous insulin infusion compared with multiple insulin injection therapy.

OBJECTIVE: To compare, in a long-term study, glycemic control by means of continuous subcutaneous insulin infusion (CSII or insulin pump therapy) versus multiple insulin injection therapy (MIIT) in routine clinical practice. METHODS: We identified, from a search of medical records, all active patients (N = 90) receiving CSII who had previously received MIIT. The primary objective was to compare the mean glycemic control, as documented by frequent measurements of glycosylated hemoglobin (HbA(1c)), during the 3-year period before initiation of CSII versus the mean glycemic control during the 3-year period after the first year of CSII. We included all patients for whom we had sufficient data for at least 1 year for both the pre- and post-CSII periods and only those patients who had received MIIT before CSII (N = 58). To eliminate potential biases, we excluded HbA(1c) values for the first year after initiation of CSII therapy. RESULTS: For the entire study group, the mean HbA(1c) +/- standard error for the 3-year period before insulin pump therapy (during MIIT) was 8.4 +/- 0.2% versus a mean HbA(1c) of 7.7 +/- 0.1% for the 3-year period after the first year of CSII. This 0.7% improvement in HbA(1c) was statistically significant (P = 0.001). Of the 34 patients with HbA(1c) values above 8.0% during MIIT, the mean HbA(1c) decreased from 9.2 +/- 0.2% with use of MIIT to 8.2 +/- 0.2% with CSII (P = 0.0006). In the 17 patients with HbA(1c) values above 9.0% during MIIT, the mean HbA(1c) declined from 10.0 +/- 0.3% with use of MIIT to 8.4 +/- 0.3% with CSII (P = 0.0006). CONCLUSION: We conclude that implementation of intensive insulin therapy with CSII improves glycemic control, even in patients in whom MIIT has previously been used to its maximal effect.

Blood Glucose↗

PubMedDate not supplied

Hypoglycemia as a barrier to glycemic control.

Diabetes mellitus is associated with significant morbidity and mortality derived from long-term microvascular and macrovascular complications of chronic hyperglycemia. The Diabetes Control and Complications Trial (DCCT) and the UK Prospective Diabetes Study (UKPDS) have clearly shown the benefits of intensive glycemic control for preventing or delaying the development and progression of long-term complications. However, intensive glycemic control, particularly with insulin therapy, is associated with an increased incidence of hypoglycemia, which is the major barrier to the implementation of intensive treatment from the physician's and patient's perspective. Avoiding the use of intensive treatment most often precludes optimal glycemic control. Some of the many underlying causes of hypoglycemia are defective and deficient counterregulatory responses, relative hyperinsulinization owing to a missed meal, excessive or unplanned exercise, erroneous insulin dosages, excessive insulinotropic effects of some oral secretagogues, and the failure of traditional insulin preparations to simulate the physiologic patterns of endogenous basal insulin secretion found in nondiabetic individuals. Additionally, patient involvement is critical to intensive glycemic control and should involve frequent self-monitoring of blood glucose (SMBG), adherence to treatment regimens, and knowledge of the interrelationship among physical activity, diet, and insulin. This review summarizes the current knowledge on hypoglycemia with a focus on the improvements in insulin therapy (i.e., the mealtime and basal insulin analogs) that may produce more normal physiologic insulin profiles with an attendant lower risk of hypoglycemia than that currently seen in clinical practice.

Awareness↗

PubMed1984

Effects of long-term optimization and short-term deterioration of glycemic control on glucose counterregulation in type I diabetes mellitus.

To assess the effects of glycemic control on glucose counterregulation, rates of plasma glucose recovery from hypoglycemia and counterregulatory hormonal responses were studied in 18 C-peptide-negative patients with insulin-dependent diabetes mellitus (IDDM) before and after either improvement, no change, or deterioration in glycemic control. Hypoglycemia was induced by an i.v. insulin infusion (30 mU/m2 X min for 1 h) after maintenance of euglycemia overnight with i.v. insulin. In 13 patients with long duration of IDDM (9 +/- 0.5 yr, mean +/- SEM) and initially poor glycemic control (mean diurnal blood glucose, MBG 199 +/- 8 mg/dl, ketoamine-HbA1 12.4 +/- 0.2%; nondiabetic subjects 104 +/- 4 mg/dl and 6.8 +/- 0.09%, respectively), rates of plasma glucose recovery from hypoglycemia (0.30 +/- 0.01 versus 0.60 +/- 0.01 mg/dl X min in nondiabetic subjects, P less than 0.001) and plasma glucagon (AUC 0.56 +/- 0.09 versus 6.3 +/- 0.50 ng/ml X 150 min in nondiabetic subjects, P less than 0.01) and epinephrine (AUC 16.9 +/- 0.2 versus 25.7 +/- 0.2 ng/ml X 150 min in nondiabetic subjects, P less than 0.001) responses to hypoglycemia were impaired. Intensive therapy (three daily injections of insulin) instituted in 7 out of 13 IDDM patients for up to 9 mo improved MBG (124 +/- 6 mg/dl, P less than 0.01) and ketoamine-HbA1 (7.9 +/- 0.02%, P less than 0.01) but not rates of plasma glucose recovery (0.31 +/- 0.01 mg/dl X min) and plasma glucagon (AUC 0.69 +/- 0.07 ng/ml X 150 min) and epinephrine (AUC 14.9 +/- 0.17 ng/ml X 150 min) responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1998

Improved glycemic control in intensively treated type 1 diabetic patients using blood glucose meters with storage capability and computer-assisted analyses.

OBJECTIVE: To determine the effect on glycemic control in intensively treated type 1 diabetic patients using a blood glucose meter with storage capability and computer-assisted analyses. RESEARCH DESIGN AND METHODS: Glycemic control was assessed in 22 intensively treated adults with type 1 diabetes for 12 months while using a meter without memory, followed by 12 months while using a meter with memory. Log books were used to assist patients in managing aspects of the diabetes treatment plan during the first 12-month period, and computer-assisted analyses were used when the meter with memory was used. GHb levels were measured monthly throughout the 24 months of observation. RESULTS: The mean GHb level averaged across all patients during the period of memory meter use (6.4%) was significantly lower than that during the period of meter use without memory (6.9%) (P=0.0004). The change in GHb levels from each period-specific baseline level occurred at significantly different slopes (P=0.046) when adjusted for baseline GHb level. In addition, the downward trend in GHb level was greater in those patients who increased the frequency of testing the most (r=-0.54, P=0.01). CONCLUSIONS: Use of a meter with memory in conjunction with computer-generated analyses of stored blood glucose test results can lead to improved glycemic control when used by a group of intensively treated adult diabetic patients. Improvement in glycemic control was related to frequency of blood glucose testing.

Adult↗

PubMed1997

Disparity in glycemic control and adherence between African-American and Caucasian youths with diabetes. Family and community contexts.

OBJECTIVE: To describe sociodemographic, family, and community factors that contribute to the glycemic control of African-American and Caucasian youths with diabetes, we investigated two questions: 1) Is there a disparity in glycemic control between African-American and Caucasian youths with diabetes, and if so, what sociodemographic, family, and community factors explain the disparity? and 2) Is there a difference in the adherence to treatment between African-American and Caucasian youths with diabetes, and if so, what sociodemographic, family, and community factors explain the difference? RESEARCH DESIGN AND METHODS: This cross-sectional study included 146 youths with diabetes (95 Caucasians and 51 African-Americans) and their mothers. The youths were invited to participate if they had been diagnosed with diabetes at least 1 year before the study, did not have another chronic illness, and were < 18 years of age. RESULTS: The findings indicate that African-American youths with diabetes are in significantly poorer metabolic control than their Caucasian counterparts (1.5% difference in HbA1c levels). Single-parent household status and lower levels of adherence partially account for the poorer glycemic control. Examination of the adherence subscales indicates that African-Americans report significantly lower adherence to diet and glucose testing than Caucasian youths. CONCLUSIONS: This study suggests that African-American youths with diabetes may be at greater risk for poor glycemic control due to the higher prevalence of single parenting and lower levels of adherence found in this population.

Adolescent↗

PubMed1984

Urinary kallikrein excretion in insulin-dependent diabetes mellitus and its relationship to glycemic control.

The renal kallikrein-kinin system is thought to be involved in vasoregulatory and epithelial ion-transporting processes. Renal kallikrein has not been studied in patients with diabetes mellitus, a disease in which abnormalities of renal hemodynamics and electrolyte handling occur. The urinary excretion of this kallikrein was measured in 20 type I diabetic patients and 10 normal subjects. On a 120-meq Na diet, daily kallikrein excretion, determined by both esterase activity and direct RIA, in 12 poorly controlled diabetic patients [hemoglobin A1c (HbA1c) = 14.2 +/- 0.5% (mean +/- SEM)] was significantly greater (P less than 0.05) than excretion in 8 diabetic patients in good to moderately good control (HbA1c = 9.4 +/- 0.5%) or in 10 normal subjects. In these groups, urinary esterase activities were 9.4 +/- 1.0, 6.1 +/- 1.4, and 6.7 +/- 0.5 esterase units/24 h, respectively. Corresponding excretion values of immunoreactive kallikrein were 171 +/- 14, 118 +/- 26, and 123 +/- 11 micrograms/24 h. Creatinine clearances were similar in the three groups. Urinary kallikrein was also measured in 8 diabetic and 8 normal subjects during 7 subsequent days of 10 meq Na intake. It increased less in diabetic patients than in normal subjects during Na depletion (P less than 0.02). The increase in urinary kallikrein in the diabetic patients was inversely related to their HbA1c levels (r = 0.88; P less than 0.01). The effect of glycemic control on urinary kallikrein excretion was determined in nine diabetic patients. Initial glycemic control was achieved using an artificial endocrine pancreas (Biostator) and was maintained by continuous sc insulin infusion with a portable pump. Before glycemic control, urinary kallikrein was 190 +/- 30 micrograms/24 h (by RIA). After 8-12 days of glycemic control, excretion fell to 144 +/- 23 micrograms/24 h (P less than 0.02). The abnormalities in kallikrein excretion in diabetic patients were not correlated with differences in water, electrolyte, protein, glucose, or aldosterone excretion in any of the studies. These results show that kallikrein excretion was increased in patients with poorly controlled insulin-dependent diabetes, and excretion rose less in diabetic subjects with low Na intake than in normal subjects. Strict glycemic control decreased urinary kallikrein excretion. These findings suggest that the renal kallikrein-kinin system is functioning abnormally in diabetes mellitus.

Adult↗

PubMedDate not supplied

Effects of improved glycemic control on microalbuminuria in adolescents with insulin-dependent diabetes mellitus.

The effect of improved glycemic control on microalbuminuria was evaluated longitudinally in 13 adolescents with insulin-dependent diabetes mellitus (IDDM) of 8.4 +/- 0.8 years duration. Glycemic control and microalbuminuria were assessed under three treatment regimens: conventional therapy (Period A); after 6 weeks of intensified conventional therapy (Period B); and at three periods during continuous subcutaneous insulin infusion (CSII) (Period C = 10-14 days, Period D = 2-4 months, and Period E = 6-8 months, of CSII). Although euglycemia was not achieved, there was a decrease in mean 24-hour blood glucose concentrations measured hourly in the hospital, with values averaging 239 mg/dl in Period A, 202 mg/dl in Period B, and 156-184 mg/dl in Periods C to E. This was accompanied by significant reductions in the values for whole blood, and to a lesser extent, in stable glycosylated hemoglobin A1 (GHbA1) (p less than 0.05), but not in creatinine clearance, albumin clearance, or in albumin excretion rate. Significant correlations were found between whole blood GHbA1 levels and albumin clearance in each of Periods B to E and between albumin clearance and albumin excretion in Periods B to D (p less than 0.05) but not in Period A. Our data suggests that the degree of improvement in glycemic control obtained in our adolescent population with IDDM using either intensive conventional therapy or CSII does not reduce the microalbuminuria. If modulation of microalbuminuria is achievable it may require euglycemia or may involve other factors which have a more direct effect on the transit of albumin across the glomerular basement membrane.

Adolescent↗