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PubMed1987

Validation of closed-loop subcutaneous insulin infusion algorithm--application of subcutaneous insulin absorption kinetics.

For long-term glycemic normalization with a closed-loop control system, a subcutaneous insulin infusion algorithm has been developed based on the pharmacokinetics of subcutaneously administered insulin. A 3-compartmental model was applied to mathematically express the relation between the insulin injected subcutaneously as an input and the plasma insulin response as an output. A computer simulation study using this model showed that the following insulin infusion algorithm is feasible for closed-loop glycemic control by selecting appropriate parameters (Kp/Kd/Kc = 0.0056/0.92/-0.11), IIR(t) = Kp G(t)+Kd d G(t)/dt+Kc, where IIR(t) is the subcutaneous insulin infusion rate at time t (min), G(t) is the blood glucose concentration and Kp, Kd, Kc are the constants. In 5 pancreatectomized dogs, subcutaneous insulin infusion with this algorithm made it possible to keep postprandial glycemic levels after oral glucose load (2 g/kg) at 168 +/- 14 mg/dl (mean +/- SEM) in 60 min and maintained normoglycemia from 180 to 300 min with the total amount of infused insulin being 0.14 +/- 0.019 U/kg. In 5 insulin-dependent diabetic patients, the peaks of postprandial glycemic levels after meal load (450 kcal) were controlled to 176 +/- 36 mg/dl at 90 min and were reduced to 98 +/- 13 mg/dl at 300 min with the total amount of infused insulin being 0.172 +/- 0.063 U/kg. The mean peak plasma insulin level was 49 +/- 11 microU/ml at 90 min. These results indicate the clinical controllability of postprandial glycemia with the closed-loop subcutaneous insulin infusion algorithm in diabetic patients.

Algorithms↗

PubMedDate not supplied

Correlation between dizziness and impaired glucose metabolism.

INTRODUCTION: Impaired glucose metabolism is characterized by conditions of hypo and hyperglycemia. AIM: The objective of the present study was to asses whether or not there is a relationship between impaired glucose metabolism and dizziness. In the clinical laboratory settings, patients were examined using vectoelectronystagmography in association with glycemic levels. METHODS: 33 patients were divided in 3 groups: diabetics; patients with dizziness and a control group. RESULTS: 65% of the patients with dizziness showed impaired glucose metabolism. 40% of the patients with dizziness had alterations in their vectoelectronystagmography results. CONCLUSION: Dizziness is a good indicator of glucose metabolism alterations and these may be a good indicator of alterations in vectoelectronystagmography responses. The study of glycemic levels after glucose overexposure is a good prognosis factor to evaluate dizziness and shows the same results as insulin level studies after glucose overexposure.

Adult↗

PubMed1995

Dietary intakes by levels of glycemic control for black and white adults with non-insulin dependent diabetes mellitus (NIDDM).

OBJECTIVES: The relationship between diet and glycemic control was examined among a racially mixed population of male and female adults with non-insulin dependent diabetes mellitus (NIDDM). METHODS: Data from 3-day dietary records and glycosylated hemoglobin (HbA1c) were analyzed for two-hundred eighty two patients of a Family Practice Ambulatory Care Unit and a community-based health center in Winston-Salem, North Carolina. Correlations were calculated for individual nutrients to determine their strength of association with glycemic control. Analyses by tertiles of HbA1c were also conducted for each race/gender group. Regression analysis was used to determine independent dietary predictors of HbA1c. RESULTS: For all subjects, energy, energy per kilogram of body weight, fat, carbohydrates saturated fat, and cholesterol were significantly correlated with HbA1c. Nutritional differences across tertile levels of HbA1c for all subjects were not significant. For black females, consumption of energy, protein and fat was significantly higher among upper tertile subjects compared to the lowest tertile; and intake of energy, protein, fat, and saturated fat was significantly correlated with HbA1c in this group. For black males, energy intake was highest among upper tertile subjects compared to those in the middle tertile, while energy per kilogram of body weight, and percent of calories from protein, were significantly correlated with HbA1c. For white males, energy intake expressed as a function of body weight was highest among subjects in the upper tertile and a significant positive correlation with HbA1c was observed. No relationship between nutritional intake and HbA1c was found among white females. Racial differences in nutrient intake were also compared for males and females in the upper tertile of HbA1c. Black females in the upper tertile consumed significantly more energy, protein, and significantly less dietary fiber per 1000 kilocalories. No significant differences were observed between black and white males in the upper tertile, although higher cholesterol consumption in black males compared to white males approached significance. Regression analysis revealed that total energy intake significantly predicted HbA1c for all subjects and all white subjects, while a similar observation was made for total fat intake among all black subjects and among black females. CONCLUSIONS: These findings confirm that diet, especially total energy, is an important contributor to glycemic control. Dietary fat is also associated with glycemic control among blacks, especially black females, who are especially prone to more dire health consequences of NIDDM. Strict monitoring of diet should lead to improved glycemic control and less mortality and morbidity in this population.

Adult↗

PubMed2003

Association of the ACP1 genotype with metabolic parameters upon initial diagnosis of type 1 diabetes.

BACKGROUND: ACP1, also called cLMWPTP (cytosolic Low Molecular Weight PTPase) is a highly polymorphic enzyme involved in the modulation of signal transduction by insulin, PDGF receptors, and T-cell receptors. The enzyme is controlled by a locus on chromosome 2, with three common codominant alleles; the corresponding six genotypes show strong variations in total enzymatic activity. The purpose of our research was to determine the relationship of ACP1 with glycemic level, ketoacidosis and HbA1C in children with Type 1 diabetes. MATERIAL/METHODS: We studied 189 consecutive children with Type 1 diabetes, from the Pediatric Clinic of Sassari University. The ACP1 genotype was determined by PCR and digestion by specific restriction enzymes. RESULTS: At initial diagnosis a strong negative correlation was observed between glycemic level and ACP1 activity, with the highest levels in genotypes with low activity. Ketoacidosis and HbA1C show a similar pattern of relationship with ACP1. A comparative analysis of the data on Type 1 diabetes with previously obtained data on Type 2 diabetes shows an opposite pattern of relationship between ACP1 and metabolic parameters. Moreover, correlation between glycemia and HbA1C in Type 1 diabetes is much weaker than in Type 2 diabetes. CONCLUSIONS: These differences suggest that the enzyme might be involved in different signal transduction pathways relevant in the pathogenesis of these two classes of diabetic disorders. It would be interesting to study the possible correlation in Type 1 diabetes between ACP1 and immunological parameters.

Base Sequence↗

PubMed1991

Insulin secretion and islet endocrine cell content at onset and during the early stages of diabetes in the BB rat: effect of the level of glycemic control.

Although it is agreed that autoimmune destruction of pancreatic islets in diabetic BB rats is rapid, reports of endocrine cell content of islets from BB diabetic rats at the time of onset of diabetes vary considerably. Because of the rapid onset of the disease (hours) and the attendant changes in islet morphology and insulin secretion, it was the aim of this study to compare islet beta-cell numbers to other islet endocrine cells as close to the time of onset of hyperglycemia as possible (within 12 h). As it has been reported that hyperglycemia renders the beta cell insensitive to glucose, the early effects of different levels of insulin therapy (well-controlled vs. poorly controlled glycemia) on islet morphology and insulin secretion were examined. When measured within 12 h of onset, insulin content of BB diabetic islets, measured by morphometric analysis or pancreatic extraction, was 60% of insulin content of control islets. Despite significant amounts of insulin remaining in the pancreas, 1-day diabetic rats exhibited fasting hyperglycemia and were glucose intolerant. The insulin response from the isolated perfused pancreas to glucose and the glucose-dependent insulinotropic hormone, gastric inhibitory polypeptide (GIP), was reduced by 95%. Islet content of other endocrine peptides, glucagon, somatostatin, and pancreatic polypeptide, was normal at onset and at 2 weeks post onset. A group of diabetic animals, maintained in a hyperglycemic state for 7 days with low doses of insulin, were compared with a group kept normoglycemic by appropriate insulin therapy. No insulin could be detected in islets of poorly controlled diabetics, while well-controlled animals had 30% of the normal islet insulin content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Serum C-peptide levels determine glycemic responses in type II diabetic patients treated with combined insulin and sulfonylurea agent.

Type II diabetes mellitus is a heterogeneous disease. Selection of either insulin or a sulfonylurea agent in addition to diet is usually made empirically. In patients who fail to respond to either agent alone, the potential benefit of combined insulin and sulfonylurea therapy is unclear. We therefore evaluated nine poorly controlled insulin treated type II diabetic patients after addition of a sulfonylurea agent--glyburide--for four weeks. Glycosylated hemoglobin (HbA1c), serum glucose, and C-peptide responses to oral glucose were evaluated. Based on a reduction of at least 50 mg/dl in the fasting serum glucose (FSG) at the end of the first week of the combination therapy or a FSG of less than 140 mg/dl, two groups were arbitrarily identified: responders (n = 5) and nonresponders (n = 4). Clinical characteristics including mean age, weight, duration of diabetes, daily dose of insulin, and duration of insulin treatment were not statistically different between the two groups. Mean baseline FSG and HbA1c levels were also not statistically different in both groups. An improvement in mean FSG and glucose tolerance occurred in the responders at the end of four weeks of combined therapy (FSG: 291 +/- 25 vs. 189 +/- 6 mg/dl, p less than 0.05; HbA1c 10.76 +/- 0.80 vs. 9.40 +/- 0.21%, p = NS). The nonresponders had no change in glucose tolerance. The mean fasting and stimulated serum C-peptide levels were significantly higher in the responders at week 4 compared with that of the nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1979

Glycosylated hemoglobins and diabetes mellitus.

Glycosylated hemoglobins result from post-translational changes in the hemoglobin molecule, and their levels correlate well with glycemic levels over the previous six to 10 weeks. Their use as an aid in monitoring diabetic control appears to be well established, but their value in predicting complications of diabetes and in diagnosing milder forms of diabetes is as yet unknown. Of the numerous methods available for the analysis of glycosylated hemoglobins, none has been evaluated extensively in a routine laboratory setting. However, liquid chromatography, isoelectric focusing, and radioimmunoassay techniques all give adequate results. For the purposes of monitoring long term diabetic control, assay of the fast hemoglobin fraction (AIa+b+c) appears adequate. However, for investigative purposes, when optimal sensitivity may be required, specific measurement of hemoglobin AIc is recommended.

Adult↗

PubMedDate not supplied

Utility of a Web-based intervention for individuals with type 2 diabetes: the impact on physical activity levels and glycemic control.

Despite the numerous benefits of physical activity for patients with diabetes, most healthcare providers in busy clinical settings rarely find time to counsel their patients about it. A Web-based program for healthcare providers can be used as an effective counseling tool, when strategies are outlined for specific stages of readiness for physical activity. Seventy-three adults with type 2 diabetes were randomly assigned to Web-based intervention, printed-material intervention, or usual care. After 12 weeks, the effects of the interventions on physical activity, fasting blood sugar, and glycosylated hemoglobin were evaluated. Both Web-based and printed material intervention, compared with usual care, were effective in increasing physical activity (P < .001) and decreasing fasting blood sugar (P<.01) and glycosylated hemoglobin (P < .01). Post hoc analysis for change scores indicated significant differences between Web-based intervention and usual care and between printed material intervention and usual care, but not between web-based and printed material intervention. The findings of this study support the value of Web-based and printed material interventions in healthcare counseling. With increasing Web access, the effectiveness of Web-based programs offered directly to patients needs to be tested.

Analysis of Variance↗

PubMed2003

Randomized, controlled, 48-week study of switching stavudine and/or protease inhibitors to combivir/abacavir to prevent or reverse lipoatrophy in HIV-infected patients.

OBJECTIVE: HIV-1 protease inhibitors (versus no protease inhibitors) and stavudine (versus zidovudine) are independently associated with a higher risk of lipoatrophy in HIV-infected patients. We sought to determine whether the revision of stavudine and/or protease inhibitor-containing regimens to combivir/abacavir would result in prevention and/or reversibility of lipoatrophy in HIV-1-infected patients. DESIGN: The investigation was a prospective, randomized, controlled, open-label study. SUBJECTS: The subjects included 37 HIV-1-infected individuals with stable undetectable HIV-1 loads who were taking a regimen containing either stavudine or zidovudine with lamivudine and a protease inhibitor. INTERVENTION: Subjects were randomized to continue therapy or switch stavudine to zidovudine and protease inhibitor to abacavir, such that the universal switch regimen was combivir (zidovudine/lamivudine) and abacavir. MAIN OUTCOME MEASURES: Total body, leg, and arm fat mass was measured at baseline, 24 weeks, and 48 weeks using whole-body dual-energy x-ray absorptiometry. Single-cut L4 computed tomography and assays of multiple metabolic parameters were also performed. RESULTS: There was an average gain in fat mass of 0.009 kg/(leg.mo) in switch patients versus a loss of 0.010 kg/(leg.mo) in controls (p =.04, on-treatment analysis) over 48 weeks. Significant arm fat restoration was observed in patients who switched regimens, with an average gain of 0.014 kg/(arm.mo) (p =.004), whereas controls did not have a significant change from baseline. Analyses of percentage changes in arm and leg fat masses showed similar findings. No significant effects on intraabdominal fat, blood lipid levels, glycemic indices, and lactate levels were detected, although most baseline mean values were normal in study subjects. Combivir/abacavir maintained virological control in all but one case, and three (13.6%) of 22 individuals had adverse reactions to abacavir therapy. CONCLUSIONS: A switch to combivir/abacavir therapy was associated with objective evidence of limb fat-sparing and fat restoration compared with continued treatment with stavudine and/or protease inhibitor.

Adult↗

PubMed1997

Comparison of a carbohydrate-rich diet and diets rich in stearic or palmitic acid in NIDDM patients. Effects on lipids, glycemic control, and diurnal blood pressure.

OBJECTIVE: To compare the effects on lipid levels, glycemic control, and diurnal blood pressure of two diets rich in one of the two quantitatively most important saturated fatty acids, stearic and palmitic acid, with a carbohydrate-rich diet in NIDDM patients. RESEARCH DESIGN AND METHODS: A total of 15 NIDDM patients participated in a randomized crossover study with three 3-week diet interventions separated by 2-week washout periods. Patients started with a diet rich in stearic acid (44 E% [percent of total energy] fat [13 E% stearic acid], 40 E% carbohydrate, 15 E% protein), palmitic acid (45 E% fat [16 E% palmitic acid], 40 E% carbohydrate, 15 E% protein), or carbohydrate (29 E% fat, 51 E% carbohydrate, and 18 E% protein), then were shifted to the other two diets in a randomized block design. At the start and end of each intervention period, fasting blood samples were drawn for analysis of lipids and blood glucose. In addition, diurnal blood pressure was measured. RESULTS: At the end of the 3-week interventions, total cholesterol was significantly higher after the palmitic acid-rich diet than after the stearic acid-rich or carbohydrate-rich diets (5.3 +/- 1.3 vs. 5.0 +/- 1.2 and 4.9 +/- 1.2 mmol/l, respectively; P = 0.03). No significant differences in triglyceride, LDL, or HDL cholesterol levels were seen after the three intervention diets. No difference in effects between the diet periods were seen for fructosamine, HbA1c, fasting blood glucose, or diurnal blood pressure. CONCLUSIONS: For the first time, it has been demonstrated that a diet rich in palmitic acid was not as effective in lowering cholesterol levels as carbohydrate-rich and stearic acid-rich diets in NIDDM patients. No deleterious effects were seen on diurnal blood pressure, triglyceride levels, and glycemic control. Development of foods containing stearic acid rather than the more atherogenic saturated fatty acids may allow a wider choice of acceptable foods to NIDDM patients.

Adult↗

PubMed2001

Fish oil in people with type 2 diabetes mellitus.

BACKGROUND: People with type 2 diabetes mellitus are at increased risk from cardiovascular disease. Dietary fish oils are known to reduce triglyceride levels, but their impact on cholesterol levels, glycemic control and vascular outcomes are not well known. OBJECTIVES: To determine the effects of fish oil supplementation on cardiovascular outcomes, cholesterol levels and glycemic control in people with type 2 diabetes mellitus. SEARCH STRATEGY: We carried out a comprehensive search of the Cochrane Controlled Trials Register, Medline, Embase, Lilacs, bibliographies of relevant papers and contacted experts for identifying additional trials. Date of last search: September 2000. SELECTION CRITERIA: All randomized placebo-controlled trials in which fish oil supplementation was the only intervention in people with type 2 diabetes were included. Authors were contacted for missing information. DATA COLLECTION AND ANALYSIS: Three investigators performed data extraction and quality scoring independently with discrepancies resolved by consensus. MAIN RESULTS: Eighteen trials including 823 participants followed for a mean of 12 weeks were included. Doses of fish oil used ranged from 3 to 18 g/day. No trials with vascular event or mortality endpoints were identified. The outcomes studied were glycemic control and lipid levels. Meta-analysis of pooled data demonstrated a statistically significant effect of fish oil in lowering triglycerides by 0.56 mmol/l (95% CI -0.71 to -0.40 mmol/l) and raising LDL cholesterol by 0.21 mmol/l (95% CI 0.02 to 0.41 mmol/l). No statistically significant effect was observed for fasting glucose, HbA1c, total or HDL cholesterol. The triglyceride lowering effect and the elevation in LDL cholesterol were most marked in those trials that recruited people with hypertriglyceridemia and used higher doses of fish oil. No adverse effects of the intervention were reported. REVIEWER'S CONCLUSIONS: Fish oil supplementation in type 2 diabetes lowers triglycerides, may raise LDL cholesterol (especially in hypertriglyceridemic patients on higher doses of fish oil) and has no statistically significant effect on glycemic control. Trials with vascular event or mortality defined endpoints are needed.

Cholesterol, LDL↗

PubMed1995

Clinically significant macular edema in type I diabetes. Incidence and risk factors.

PURPOSE: To examine incidence of and risk factors for clinically significant macular edema in persons with type I diabetes. METHODS: A group of 189 persons with type I diabetes, recruited from a summer camp for children with diabetes and from practices of local physicians, were participants in a longitudinal study with annual follow-up visits which included physical and ophthalmologic examinations and color stereo fundus photographs of each eye, centered on the disc and macula. Subjects were free of proliferative retinopathy at study baseline. Ages ranged from 3 to 40 years, duration of diabetes ranged from 0 to 12 years, mean glycosylated hemoglobin (Hgb A1c) was 12.2% (range, 6.4%-21.5%), and average follow-up was 6.1 years. Presence of clinically significant macular edema was defined as in the Early Treatment Diabetic Retinopathy Study. RESULTS: In a total of 41 persons (62 eyes), clinically significant macular edema developed during study follow-up. Cumulative risk of clinically significant macular edema was 0 until 7 years' duration of diabetes. The cumulative risk of clinically significant macular edema increased linearly for each year of duration between 10 and 20 years, with an average annual increase of approximately 6.7%. Significant risk factors for clinically significant macular edema were older age at diagnosis, male sex, and higher Hgb A1c level. Systolic and diastolic blood pressure, proteinuria, body mass index, race, initial presence of retinopathy, and use of antihypertensives did not significantly affect the risk of clinically significant macular edema. CONCLUSION: Older age at diagnosis of diabetes, male sex, and higher Hgb A1c levels (poorer control of blood glycemic levels) significantly increase the risk of clinically significant macular edema in persons with type I diabetes. These data extend the evidence implicating worse glycemic control as a cause of clinically significant macular edema, even within a population with relatively loose control.

Adolescent↗

PubMed1994

Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. A double-blind controlled study.

OBJECTIVE: To assess and compare the therapeutic efficacy and safety of metformin (M) and sulfonylurea (glyburide, G), alone and in various combinations, in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Of 165 patients (fasting blood glucose [FBG] > or = 6.7 mmol/l) initially treated with diet alone, 144 (FBG still > or = 6.7 mmol/l) were randomized to double-blind, double-dummy controlled treatment with M, G, or primary combination therapy (MG). The dose was titrated, with FBG < 6.7 mmol/l as target, using, at most, six dose levels. The first three dose levels comprised increasing single-drug therapy (M or G) or primary combination at increasing but low dosage (MGL), and the second three levels were composed of various high-dose combinations, i.e., add-on therapy (M/G or G/M) and primary combination escalated to high dosage (MGH). Medication was maintained for 6 months after completed dose titration. RESULTS: The FBG target was achieved in 9% of patients after diet alone. Single-drug therapy was insufficient in 36% and MGL in 25% (NS) of the randomized patients. There was further improvement in glucose control by the high-dose combinations. Mean FBG +/- SE was reduced (P = 0.001) from 9.1 +/- 0.4 to 7.0 +/- 0.2 mmol/l in those maintained on single-drug treatment or low-dose primary combination. Those treated with different high-dose combinations had a large mean FBG reduction, from 13.3 +/- 0.8 to 7.8 +/- 0.6 mmol/l. HbA1c levels showed corresponding reductions, and glycemic levels rose after drug discontinuation. Fasting C-peptide rose during treatment with G and MGL but not with M, while fasting insulin was not significantly changed. Meal-stimulated C-peptide and insulin levels were unchanged by M but increased by G and, to a lesser extent, by MGL. There were no significant insulin or C-peptide differences between the different high-dose combinations (M/G, G/M, and MGH). Body weight did not change following treatment with M or combination but increased by 2.8 +/- 0.7 kg following G alone. Blood pressure was unchanged. Overall effects on plasma lipids were small, with no significant differences between groups. Drug safety was satisfactory, even if the reporting of (usually modest) adverse events was high; the profile, but not the frequency, differed between groups. CONCLUSIONS: Dose-effect titrated treatment with either metformin or glyburide promotes equal degrees of glycemic control. The former, but not the latter, is able to achieve this control without increasing body weight or hyperinsulinemia. Near-normal glycemia can be obtained by a combination of metformin and sulfonylurea, even in advanced NIDDM.

Adult↗

PubMed1994

Toxicity of insulin administered chronically to human eye in vivo.

Insulin administered in eyedrop from with a surfactant agent has been shown to be clinically effective in treating diabetes in animal models. Concentrations of insulin as high as 100 U/ml in saline were shown to produce no detectable clinical toxicity to human eyes in single-dose administration. We sought to investigate the local toxicity of insulin in human eyes during long-term, multidose administration. A prospective, randomized, placebo controlled, double-masked study was conducted involving eight healthy volunteers. Subjects were given 50 microliters sterile saline containing 100 U/ml crystalline porcine insulin randomized to one eye and 50 microliters placebo (sterile saline) to the fellow eye administered twice daily for 8 weeks. Subjective ocular irritation and visual acuity and objective assessment of the eyelids, conjunctiva, cornea, anterior chamber, crystalline lens, pupil size, and intraocular pressure were evaluated. Blood D-glucose levels were monitored to assess glycemic levels. There was no statistically significant difference (p > 0.05) observed between insulin-treated and placebo-treated eyes. Eyedrops containing insulin were subjectively as comfortable and objectively as clinically innocuous as sterile saline alone. The results of this study demonstrate that insulin (100 U/ml) in saline is nontoxic to the human eye after long-term, multi-dose exposure. Topical administration of insulin combined with an absorption-promoting agent may be a practical and feasible alternative to multiple daily subcutaneous injections or implanted pump devices currently used in the long-term treatment of diabetes mellitus if a nonirritating absorption-promoting agent can be identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1999

Pharmacologic therapy for type 2 diabetes mellitus.

Type 2 diabetes mellitus is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. An elevated rate of basal hepatic glucose production in the presence of hyperinsulinemia is the primary cause of fasting hyperglycemia; after a meal, impaired suppression of hepatic glucose production by insulin and decreased insulin-mediated glucose uptake by muscle contribute almost equally to postprandial hyperglycemia. In the United States, five classes of oral agents, each of which works through a different mechanism of action, are currently available to improve glycemic control in patients with type 2 diabetes. The recently completed United Kingdom Prospective Diabetes Study (UKPDS) has shown that type 2 diabetes mellitus is a progressive disorder that can be treated initially with oral agent monotherapy but will eventually require the addition of other oral agents, and that in many patients, insulin therapy will be needed to achieve targeted glycemic levels. In the UKPDS, improved glycemic control, irrespective of the agent used (sulfonylureas, metformin, or insulin), decreased the incidence of microvascular complications (retinopathy, neuropathy, and nephropathy). This review examines the goals of antihyperglycemic therapy and reviews the mechanism of action, efficacy, nonglycemic benefits, cost, and safety profile of each of the five approved classes of oral agents. A rationale for the use of these oral agents as monotherapy, in combination with each other, and in combination with insulin is provided.

Acarbose↗

PubMed2006

Effects of hyperglycemia on the differential expression of insulin and insulin-like growth factor-I receptors in human normal peritoneal and adhesion fibroblasts.

OBJECTIVE: To determine whether the insulin receptor (IR), insulin-like growth factor-I receptor (IGF-IR), and IGF-I are expressed differentially in fibroblasts isolated from normal peritoneal and adhesion tissue before and after 24-hour treatment with increasing glucose concentrations. DESIGN: Prospective experimental study. SETTING: University medical center. PATIENT(S): Primary cultures of fibroblasts established from peritoneal and adhesion tissues of the same patients. INTERVENTION(S): Glucose treatment of the primary cultured fibroblasts for 24 hours with increasing concentrations of glucose (100-850 mg/dL). MAIN OUTCOME MEASURE(S): Real-time polymerase chain reaction was used to measure messenger RNA (mRNA) levels for IR, IGF-IR, and IGF-I. Enzyme-linked immunosorbent assay was used to determine protein levels. RESULT(S): At the normal glycemic level (100 mg/dL), adhesion fibroblasts have significantly higher mRNA levels of the IR (7.96 +/- 0.15 vs. 6.97 +/- 0.16; P<.05), IGF-IR (7.72 +/- 0.22 vs. 6.88 +/- 0.06; P<.05), and IGF-I (7.04 +/- 0.10 vs. 5.92 +/- 0.10; P<.05) when compared with normal fibroblasts, respectively. Data are expressed as log(mRNA/microg RNA). Normal fibroblasts respond to increasing glucose concentrations by increasing the expression levels of the IR, IGF-IR, and IGF-I, whereas adhesion fibroblasts respond by decreasing the expression of the IR, IGF-IR, and IGF-I. CONCLUSION(S): The differential expression of the IR, IGF-IR, and IGF-I in adhesion fibroblasts may contribute to the pathogenesis of fibrosis observed in diabetic patients.

Cells, Cultured↗

PubMed1982

Short term improvement in glycemic control utilizing continuous subcutaneous insulin infusion: the effect on 24-hour integrated concentrations of counterregulatory hormones and plasma lipids in insulin-dependent diabetes mellitus.

Eight patients with established insulin-dependent diabetes mellitus were studied before and 2 weeks after the initiation of pumped continuous sc insulin infusion in order to investigate the effect of short term improvement of glycemic control on hormonal and lipid levels. Glycemic control was improved in all patients. Using a constant blood withdrawal pump, accurate 24-h average concentrations, denoted integrated concentrations, were obtained. The mean 24-h integrated concentrations of GH, cortisol, norepinephrine, and epinephrine did not change significantly. The mean fasting triglyceride concentration dropped from 119.1 to 83.4 mg/dl (P less than 0.05). The mean 24-h integrated concentration of plasma triglycerides fell from 132.1 to 101.5 mg/dl (P less than 0.02). Both mean fasting and mean 24-h integrated concentrations of plasma cholesterol were lower after improved control. Short term improvement in glycemic control was associated with a reduction in plasma lipid concentrations, but failed to alter mean 24-h integrated concentrations of the measured counterregulatory hormones.

Adolescent↗

PubMed1999

[Influence of intelligence level of the type I diabetic patients handling hi-tech glycemia monitoring system on the effectiveness of intensive insulin treatment].

An intensive care system designed and developed in IBBE PAS allows for electronic storage and automatic transmission of BG values and other parameters directly from a patient's BG meter and electronic logbook (Glucometer M+ Bayer) to central clinical computer by telematic connection. Despite effort made to keep the system as simple as possible, its proper handling still requires some additional skills from the patient. Thus, effectiveness of the intensive insulin treatment supported by the system may be influenced by the patient's intelligence level. The aim of this work was to evaluate influence of the intelligence level of type 1 diabetic patients equipped with designed system on effectiveness of a long-term intensive insulin treatment. The study group consisted of 17 type 1 diabetic pregnant women randomly divided in two sub-groups. Eight patients used the transmission system and the remaining 9 patients were treated classically. Patient's intelligence level was assessed according Wechsler scale. Analysis of variance indicated that intelligence level did not influence significantly on average result of the treatment (p > 0.05) in whole study group and in both subgroups. Generally, in patients with lower (93 +/- 2.0) and higher (114.1 +/- 1.2) intelligence level glycemic control indices were found to be similar and did not differ significantly. Performed analysis indicated that the designed system could be properly handled by diabetic patients within wide range of intelligence level. However, despite not statistically significant influence of the patients intelligence level on obtained glycemic control, tendency was observed to obtain better average long-term glycemic control in patients with lower intelligence level using telematic data transmission in comparison with the patients treated in classical way (SDWG = 7.0 +/- 0.4 vs. 8.1 +/- 1.0 mmol/l and J = 30.3 +/- 4.4 vs. 39.0 +/- 12.2).

Adult↗