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Periodontal status of diabetic and non-diabetic men: effects of smoking, glycemic control, and socioeconomic factors.

Periodontal disease is more prevalent and more severe in diabetic than in non-diabetic individuals but the magnitude of this increase is still being debated. This prospective, cross-sectional study compared the periodontal status of 118 diabetic men and 115 age-matched non-diabetic men. Plaque and gingival indices, bleeding scores, probing depth, loss of attachment, and number of missing teeth were measured in a blinded manner. Smoking status, glycemic control, socioeconomic status, and previous dental care were also assessed. These parameters were significantly higher in diabetic than non-diabetic men: plaque index, P < 0.0001; gingival index, P < 0.0002; bleeding score, P < 0.0001; probing depth, P = 0.0059; loss of attachment, P < 0.0001; and missing teeth, P < 0.005. These parameters were significantly higher in smokers than non-smokers: gingival index, probing depth, and loss of attachment. The duration of diabetes was not significantly related to the periodontal measures. Glycemic control as assessed by fasting plasma glucose and glycohemoglobin values was not significantly correlated to periodontal status. These studies indicate, for this study group, that diabetes significantly affects all measured parameters of periodontal status.

Adult↗

Dietary protein impact on glycemic control during weight loss.

Diets with higher protein (1.5 g x kg(-1) x d(-1)) and reduced carbohydrates (120 to 200 g/d) appear to enhance weight loss due to a higher loss of body fat and reduced loss of lean body mass. While studies of prolonged use of moderate protein diets are not available, short-term studies report beneficial effects associated with increased satiety, increased thermogenesis, sparing of muscle protein loss, and enhanced glycemic control. Combined impacts of a moderate protein diet are likely derived from lower carbohydrates resulting in lower postprandial increase in blood glucose and lower insulin response, and higher protein providing increased BCAA leucine levels and gluconeogenic substrates. A key element in the diet appears to be the higher intake of BCAA leucine with unique regulatory actions on muscle protein synthesis, modulation of the insulin signal, and sparing of glucose use by stimulation of the glucose-alanine cycle. This review focuses on the contributions of leucine and the BCAA to regulation of muscle protein synthesis and glycemic control.

Amino Acids↗

Rationale, design, and methods for glycemic control in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial.

A major therapeutic question in considering accelerated atherogenesis in patients with type 2 diabetes mellitus is whether reducing insulin resistance, as a proximal defect of a host of proatherogenic abnormalities including hyperglycemia, will be superior for decreasing mortality and coronary artery disease (CAD) risk compared with treating hyperglycemia to overcome insulin resistance with insulin-providing agents. This question is highly relevant, since earlier targeted glycemic control trials utilizing conventional glucose-lowering strategies that increase insulin levels have generally failed to reduce CAD risk despite markedly reducing microvascular risk. The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial seeks to determine whether primarily using an insulin-sensitizing strategy for treatment of type 2 diabetes is superior when compared with primarily using an insulin-providing strategy with regard to cardiovascular outcomes. This article presents the rationale, design, and methods being used to test the glycemic control hypothesis in BARI 2D.

Algorithms↗

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

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

Adult↗

Testicular function and glycemic control in diabetic men. A controlled study.

We have investigated testicular function in 28 insulin-dependent diabetic men under the age of 50 years and 119 age-matched controls. Diabetics had reduced testicular volume, semen volume, total and total motile sperm output while plasma LH and FSH levels were elevated. Reduction in semen volume and impotence were more common in long-standing complicated diabetes. Glycosylated hemoglobin (GHb) levels were positively correlated with plasma LH levels (r = 0.46, p less than 0.02) but there was no direct correlation of glycemic control and spermatogenesis. The differences in testicular function were due to decreased spermatogenesis and could not be explained by other forms of testicular pathology or the presence of diabetic neurovascular complications. We conclude that the function of the hypothalamic pituitary testicular axis is impaired in diabetic men, that this impairment is at least partly related to the degree of preceding glycemic control and that multiple levels of the axis may be dysfunctional.

Adult↗

Relationship between adiponectin and glycemic control, blood lipids, and inflammatory markers in men with type 2 diabetes.

OBJECTIVE: Adiponectin, synthesized in the adipose tissue, appears to play an important role in hyperglycemia and dyslipidemia, as well as in inflammatory mechanisms, which lead to a markedly increased atherosclerotic risk in diabetic subjects. However, previous studies did not evaluate the complex relationships between adiponectin and the array of metabolic abnormalities commonly observed in diabetes. RESEARCH DESIGN AND METHODS: To examine the associations between plasma levels of adiponectin and HbA(1c), blood lipids, and inflammatory markers, we obtained blood samples from 741 participants in the Health Professionals Follow-up Study with a diagnosis of type 2 diabetes. RESULTS: Plasma adiponectin levels were positively correlated with HDL cholesterol and negatively correlated with triglycerides, apolipoprotein B-100 (apoB(100)), C-reactive protein (CRP), and fibrinogen. These associations were not appreciably altered after controlling for lifestyle exposures, medical conditions, and obesity-associated variables. A 10-microg/ml higher level of plasma adiponectin was associated with lower HbA(1c) (-0.21% points, P = 0.001), triglycerides (-0.39 mmol/l, P < 0.001), apoB(100) (-0.04 g/l, P < 0.001), CRP (-0.51 mg/l, P = 0.003), and fibrinogen (-0.53 micromol/l, P < 0.001) and higher HDL cholesterol (0.13 mmol/l, P < 0.001). Associations between adiponectin and inflammatory markers were furthermore independent of HbA(1c) and HDL cholesterol, suggesting that the anti-inflammatory properties of adiponectin are not mediated by potential effects on glycemic control and blood lipids. Our results were consistent among obese and nonobese men. CONCLUSIONS: Our study supports the hypothesis that increased adiponectin levels might be associated with better glycemic control, better lipid profile, and reduced inflammation in diabetic subjects. Measures that increase adiponectin levels might be valuable targets for decreasing the atherosclerotic risk present in diabetes.

Adiponectin↗

Hepatic insulin action in adolescents with insulin-dependent diabetes mellitus: relationship with long-term glycemic control.

The relationship between hepatic insulin action and long-term glycemic control was assessed in 20 adolescents with insulin-dependent diabetes mellitus (IDDM) and five healthy matched controls using a two-step (0.8 and 1.6 mU/kg/min) hyperinsulinemic-euglycemic clamp and [6,6-2H2]glucose. The night before the study, diabetic patients received variable-rate intravenous insulin in an attempt to normalize fasting plasma glucose concentrations. In the postabsorptive state, hepatic glucose production (HGP) was similar in IDDM patients and controls (593 +/- 40 v 518 +/- 27 mumol/m2/min); however, plasma glucose and free insulin concentrations were higher in IDDM patients than in controls (6.5 +/- 0.4 v 5.4 +/- 0.1 mmol/L [P = .01], and 207 +/- 21 v 104 +/- 10 pmol/L [P < .001], respectively). There was a positive correlation (r = .62 P = .002) between basal HGP and glycohemoglobin level (HbA1). Separation of the patients at the median HbA1 (group no. 1 < and group no. 2. > 11.4% HbA1) revealed two distinct patient populations with regard to hepatic and peripheral insulin action and plasma free fatty acid (FFA) suppression. During hyperinsulinemia, the percent suppression of HGP was lower in group no. 2 compared with group no. 1 (65.7% +/- 9.8% v 94.4% +/- 3.8%; P = .018). Rates of glucose disposal were lower in group no. 2 compared with controls and with group no. 1. Postabsorptive FFA levels were similar between group no. 2 and group no. 1 (0.45 +/- 0.03 and 0.43 +/- 0.04 mmol/L) despite higher free-insulin concentrations in group no. 2 (260 +/- 30 v 171 +/- 25 pmol/L; P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Introduction of sucrose in the diet plan of persons with type 1 diabetes: its influence in the glycemic control].

UNLABELLED: To evaluate the influence of sucrose intake in the glycemic control, ten adolescents with type 1 diabetes were followed during eight months. Initially, they received personalized orientation on diet, self monitoring blood glucose and insulin dose adjustment; after four months, all patients introduced sucrose in their afternoon meals, through the method of carbohydrate counting. Total cholesterol and triglycerides levels were measured in the beginning and in the final of the study. Hemoglobin A1C levels were measured in the beginning, after four months without and after four months with intake of foods with sucrose. All patients showed adequate pubertal development and growth; two had overweight and the others were eutrophic. After four months of follow up, the frequency of self monitoring blood glucose was reduced (p< 0.001). Total cholesterol and triglycerides values were in the normal range and A1C values decreased during the observed period (p= 0.027). CONCLUSION: The consumption of foods with sucrose, using the technique of carbohydrate counting, did not affect the metabolic control of adolescents with type 1 diabetes.

Adolescent↗

The effect of glycemic control on plasma soluble fibrin monomer complexes and fibronectin in diabetic patients.

We have shown previously that increased concentrations of plasma soluble fibrin monomer complexes (SFMC) and elevated fibronectin (Fn) levels are closely related to the development of diabetic microangiopathy. The purpose of the present study was to explore whether or not changes in plasma glucose levels could have an effect on these protein constituents. Plasma glucose levels of 25 uncontrolled diabetic patients were brought under control with insulin and serial measurements of SFMC and Fn were made over a period of 4 weeks. Glucose values fell from an average of 312 mg/100 ml to 160 mg/100 ml. Ten patients with macroproteinuria (i.e. greater than or equal to 0.5 g/24 hr) showed initially elevated plasma SFMC and Fn concentrations. These levels fell significantly over the 4 week observation period: from 13.6 mg/100 ml to 9.4 mg/100 ml for SFMC and from 38.4 mg/100 ml to 34.5 mg/100 ml for Fn. The remaining 15 patients had nearly normal levels of both SFMC (7.9 mg/100 ml) and Fn (31.1 mg/100 ml) and glycemic control brought no further reduction. The data indicated that a) elevated SFMC and Fn levels are indeed associated with diabetic microangiopathy, especially in the presence of macroproteinuria; and b) adequate glycemic control is capable of normalizing the plasma concentration of these constituents.

Adult↗

Effects of clinical nutrition education and educator discipline on glycemic control outcomes in the Indian health service.

OBJECTIVE: We used the Indian Health Service (IHS) Diabetes Care and Outcomes Audit to assess the effectiveness of clinical nutrition education in reducing HbA(1c) levels and to test the relative effectiveness of clinical nutrition education when it was delivered by a registered dietitian (RD) compared with an educator from another discipline (non-RD). RESEARCH DESIGN AND METHODS: We examined clinical care data collected by the IHS Diabetes Care and Outcomes Audit of 7490 medical records during 2001. Glycemic control was assessed by using the difference between the two most recent HbA(1c) levels during 2001. Age, BMI, duration of diabetes, type of treatment, proteinuria, and facility were included as covariates. Clinical nutrition education was defined as documentation in the record of any diet instruction and educator discipline classified as RD or non-RD. ANCOVA methods were used to assess the effects of diet education and educator discipline on differences between the two HbA(1c) measurements and to adjust for differences in the distribution of covariates among the education groups. RESULTS: After adjustment for age, sex, type of treatment, duration of diabetes, BMI, initial HbA(1c) level, and clinical facility, clinical nutrition education and educator discipline were each associated with changes in HbA(1c) levels (P < 0.001). Those receiving clinical nutrition education from an RD or from an RD as well as a non-RD had the largest improvements in HbA(1c) levels (-0.26 and -0.32, respectively) compared with those receiving either only non-RD or no clinical nutrition education (-0.19 and -0.10, respectively). CONCLUSIONS: Clinical nutrition education in the IHS is associated with favorable trends in glycemic control. To be effective, clinical nutrition education should be delivered by an RD or a team that includes an RD.

Adult↗

Improved glycemic control in subjects with atypical diabetes results from restored insulin secretion, but not improved insulin sensitivity.

African-American subjects often present with hyperglycemic crisis (diabetic ketoacidosis or severe hyperglycemia), yet subsequently are treated without insulin. The pathophysiology of this unique condition is unknown. We hypothesized that recovery from atypical diabetes with intensive insulin therapy resulted from a reversal of a defect in beta-cell function and improved insulin sensitivity. We studied eight newly diagnosed, antibody-negative African-American subjects (age, 34-56 yr) who presented with hyperglycemic crisis. Subjects were studied at baseline after overnight glycemic control and again after 3 wk and 3 months of intensive insulin therapy. Insulin sensitivity (SI) was determined from an insulin-modified, frequently sampled i.v. glucose tolerance test, and insulin secretion was measured as the acute insulin response to glucose and to a glucagon stimulation test. Fructosamine and hemoglobin A1c declined significantly with intensive insulin therapy, and insulin requirements decreased over time. Both acute insulin response to glucose and the C peptide response to glucagon stimulation test improved by 3 wk (P = 0.02 vs. baseline), and improvements were maintained at 3 months (P = 0.02 vs. baseline). In contrast, the SI remained low throughout the study. We demonstrate that improved glycemic control correlates with a remarkable recovery of beta-cell function, but no change in SI.

Adult↗

Combined metformin-sulfonylurea treatment of patients with noninsulin-dependent diabetes in fair to poor glycemic control.

The effect of metformin treatment was studied in 13 patients with noninsulin-dependent diabetes mellitus (NIDDM), whose fasting plasma glucose concentration was greater than 10 mmol/L with maximal sulfonylurea doses. Patients were studied before and 3 months after receiving 2.5 g/day metformin. The fasting plasma glucose concentration (12.4 +/- 0.8 vs. 8.8 +/- 0.7 mmol/L), mean hourly postprandial plasma glucose concentration from 0800-1600 h (14.0 +/- 1 vs. 9.4 +/- 0.9 mmol/L), and glycosylated hemoglobin level (12.3 +/- 0.6% vs. 9.0 +/- 0.6%) were all significantly (P less than 0.005-0.001) lower after the administration of metformin. The improvement in glycemic control was associated with a 24% increase (P less than 0.05) in insulin-stimulated glucose uptake during glucose clamp studies and a 16% decrease in basal hepatic glucose production (P less than 0.05). Mean hourly concentrations of plasma insulin (411 +/- 73 vs. 364 +/- 73 pmol/L) and FFA concentrations (440 +/- 31 vs. 390 +/- 40 mumol/L) were also lower after 3 months of metformin treatment. However, neither insulin binding nor insulin internalization by isolated monocytes changed in response to metformin. Finally, plasma triglyceride, very low density lipoprotein triglyceride, and very low density lipoprotein cholesterol were significantly decreased (P less than 0.01-0.001), and high density lipoprotein cholesterol was significantly increased (P less than 0.001) after metformin treatment. Thus, the addition of metformin to sulfonylurea-treated patients with NIDDM not in good glycemic control significantly lowered fasting and postprandial plasma glucose concentrations, presumably due to the combination of enhanced glucose uptake and decreased hepatic glucose production. Since the dyslipidemia present in these patients also improved, the results suggest that metformin may be of significant clinical utility in patients with NIDDM not well controlled with sulfonylurea compounds.

Blood Glucose↗

Catalase and paraoxonase in hypertensive type 2 diabetes mellitus: correlation with glycemic control.

OBJECTIVES: Type 2 diabetes mellitus (DM) is well recognized as being associated with increased prevalence of hypertension. Experimental and epidemiologic studies have shown that oxygen-free radicals are elevated because antioxidant enzyme activities are altered both in uncontrolled essential hypertension and DM itself. Recently paraoxonase (PON) has been recognized as an antioxidant enzyme that hydrolyzes lipid peroxides. The aim of this study is to evaluate simultaneously PON activities and antioxidant status in hypertensive type 2 DM cases and to establish any possible relationship between these parameters and duration of hypertension or diabetes, hemoglobin (Hb) A1c levels, and lipid parameters. DESIGN AND METHODS: Nineteen normotensive subjects with type 2 DM, 37 hypertensive (diastolic blood pressure 90 mm Hg or more) subjects with type 2 DM, and 25 normotensive control subjects with normal glucose tolerance were selected for this study. Superoxide dismutase (SOD), catalase, and basal-stimulated PON activities were measured by the methods of Sun et al.; Goth; and Eckerson, Wyte, and La Du, respectively; other lipid parameters were determined using an autoanalyzer. RESULTS: Catalase activities of either hypertensive patients with type 2 DM or type 2 DM patients without complication were found to be higher than controls (p<0.01), although no significant difference in SOD and basal-stimulated PON activities was observed between these groups. A significant elevation in catalase activity (p = 0.004) of patients with high HbA1c levels (>7.0%) (n = 37) compared with patients with low HbA1c levels (<7.0%) (n = 19) was detected. There was also a positive correlation between the catalase activities and fasting glucose levels and HbA1c concentrations in hypertensive patients with type 2 DM (r = 0.4567, p<0.05 and r = 0.3686, p<0.05, respectively). An increase in catalase activity of patients with B and/or AB phenotype compared with patients with A phenotype was also noted. CONCLUSION: Poor glycemic control in diabetes is strongly associated with an increase in free radicals and consequent diabetic complications. Uncontrolled glucose metabolism may also be the cause of alterations in antioxidant enzymes. Among these, catalase correlates best with poor glycemic control. The current data reveal that B allele carriers of PON are more susceptible to oxidant stress.

Aged↗

Glycemic control and prognosis in type I diabetic patients with microalbuminuria.

OBJECTIVE: To investigate the course of microalbuminuria during the 1980s in type I diabetes patients. RESEARCH DESIGN AND METHODS: This was a 10-year follow-up of 109 patients in whom type I diabetes was diagnosed between 1961 and 1980 before 15 years of age and who were initially investigated between 1977 and 1983 after a diabetes duration of > or = 3 years. Microalbuminuria was defined as an albumin excretion rate (AER) of 20-200 micrograms/min in two of three consecutive urine samples. RESULTS: At the initial investigation, 81 patients had normal AER, 27 had microalbuminuria, and 1 had macroalbuminuria. Between 1989 and 1992, 99 (91%) patients were reinvestigated. Only 5 (19%) of the initially microalbuminuric patients developed macroproteinuria during the 10-year follow-up period, and in 15 (58%) patients, AER decreased to normal. Three (4%) of the normoalbuminuric patients developed microalbuminuria but none macroproteinuria. The initially microalbuminuric patients, in whom AER normalized, improved their glycemic control from 1980-1983 to 1989-1991 (mean +/- SE HbA1c 7.5 +/- 0.2 to 6.6 +/- 0.3%; P = 0.01). CONCLUSIONS: In the majority of patients with microalbuminuria in whom it is possible to obtain good glycemic control, microalbuminuria will disappear and the risk of developing nephropathy will be markedly reduced.

Adolescent↗

A nurse-coordinated intervention for primary care patients with non-insulin-dependent diabetes mellitus: impact on glycemic control and health-related quality of life.

OBJECTIVE: To examine the impact of a nurse-coordinated intervention delivered to patients with non-insulin-dependent diabetes mellitus between office visits to primary care physicians. DESIGN: Randomized, controlled trial. SETTING: Veterans Affairs general medical clinic. PATIENTS: 275 veterans who had NIDDM and were receiving primary care from general internists. INTERVENTION: Nurse-initiated contacts were made by telephone at least monthly to provide patient education (with special emphasis on regimens and significant signs and symptoms of hyperglycemia and hypoglycemia), reinforce compliance with regimens, monitor patients' health status, facilitate resolution of identified problems, and facilitate access to primary care. MEASUREMENTS: Glycemic control was assessed using glycosylated hemoglobin (GHb) and fasting blood sugar (FBS) levels. Health-related quality of life (HRQOL) was measured with the Medical Outcomes Study SF-36, and diabetes-related symptoms were assessed using patients' self-reports of signs and symptoms of hyper- and hypoglycemia during the previous month. MAIN RESULTS: At one year, between-group differences favored intervention patients for FBS (174.1 mg/dL vs 193.1 mg/dL, p = 0.011) and GHb (10.5% vs 11.1%, p = 0.046). Statistically significant differences were not observed for either SF-36 scores (p = 0.66) or diabetes-related symptoms (p = 0.23). CONCLUSIONS: The intervention, designed to be a pragmatic, low-intensity adjunct to care delivered by physicians, modestly improved glycemic control but not HRQOL or diabetes-related symptoms.

Blood Glucose↗

Skeletal muscle FOXO1 (FKHR) transgenic mice have less skeletal muscle mass, down-regulated Type I (slow twitch/red muscle) fiber genes, and impaired glycemic control.

FOXO1, a member of the FOXO forkhead type transcription factors, is markedly up-regulated in skeletal muscle in energy-deprived states such as fasting and severe diabetes, but its functions in skeletal muscle have remained poorly understood. In this study, we created transgenic mice specifically overexpressing FOXO1 in skeletal muscle. These mice weighed less than the wild-type control mice, had a reduced skeletal muscle mass, and the muscle was paler in color. Microarray analysis revealed that the expression of many genes related to the structural proteins of type I muscles (slow twitch, red muscle) was decreased. Histological analyses showed a marked decrease in size of both type I and type II fibers and a significant decrease in the number of type I fibers in the skeletal muscle of FOXO1 mice. Enhanced gene expression of a lysosomal proteinase, cathepsin L, which is known to be up-regulated during skeletal muscle atrophy, suggested increased protein degradation in the skeletal muscle of FOXO1 mice. Running wheel activity (spontaneous locomotive activity) was significantly reduced in FOXO1 mice compared with control mice. Moreover, the FOXO1 mice showed impaired glycemic control after oral glucose and intraperitoneal insulin administration. These results suggest that FOXO1 negatively regulates skeletal muscle mass and type I fiber gene expression and leads to impaired skeletal muscle function. Activation of FOXO1 may be involved in the pathogenesis of sarcopenia, the age-related decline in muscle mass in humans, which leads to obesity and diabetes.

Adenosine Triphosphatases↗

Psychologic stress and glycemic control: a comparison of patients with and without proliferative diabetic retinopathy.

Using a case/control design, patients with (cases) and without (controls) proliferative diabetic retinopathy were compared using three psychosocial measures: life events, psychiatric symptomatology, and ego development. Cases reported significantly more symptoms. They also demonstrated a modest and significant correlation of negative life events with HgbA1c that was not shown in the controls. When the relationship of life events with glycemic control was explored in cases of varying durations of proliferative retinopathy, we found that the association between negative life events and HgbA1c was accounted for by the cases with a recent onset of retinopathy. Patients in this recent group showed a trend towards more negative life events that decreased with longer duration of proliferative retinopathy. This study suggests that the onset of proliferative retinopathy portends a life crisis during which metabolic control is sensitive to additional life stress and that this association is not found among patients whose illness is more stable.

Adult↗

An implantable subcutaneous glucose sensor array in ketosis-prone rats: closed loop glycemic control.

A closed loop system of diabetes control would minimize hyperglycemia and hypoglycemia. We therefore implanted and tested a subcutaneous amperometric glucose sensor array in alloxan-diabetic rats. Each array employed four sensing units, the outputs of which were processed in real time to yield a unified signal. We utilized a gain-scheduled insulin control algorithm which rapidly reduced insulin delivery as glucose concentration declined. Such a system was generally effective in controlling glycemia and the degree of lag between blood glucose and the sensor signal was usually 3-8 min. After prolonged implantation, this lag was sometimes longer, which led to impairment of sensor accuracy. Using a prospective two-point calibration method, sensor accuracy and closed loop control were good. A revised algorithm yielded better glycemic control than the initial algorithm did. Future research needs to further improve calibration methods and reduce foreign body fibrosis in order to avoid a time-related increase in lag duration.

Algorithms↗