Well-controlled Diabetes Mellitus Research Articles

Wavelike Epitheliopathy After Phacoemulsification

The purpose of this report was to describe an uncommon wavelike epitheliopathy after phacoemulsification in a 59-year-old man with well-controlled diabetes mellitus. Retrospective case report. A 59-year-old man with a history of well-controlled diabetes mellitus presented to us with irritation and blurring of vision in the right eye of 4-month duration after phacoemulsification with multifocal intraocular lens implantation. Slit-lamp examination revealed a wave-like epitheliopathy in the right cornea, extending nasally from the incision area. Corneal sensation was reduced. Confocal microscopy revealed reduced subbasal nerve plexus and unhealthy corneal epithelium. Topical application of preservative-free lubricants was advised. On follow-up examinations, it was observed that the disappearance of the epitheliopathy correlated with the regeneration of the nerve plexus, as shown by the in vivo confocal microscopy findings. This is an isolated case report of a wavelike epitheliopathy after phacoemulsification. The regeneration of the subbasal nerve plexus correlating with the disappearance of the epitheliopathy suggests an element of neurotrophic corneal damage. Other probable mechanisms are discussed along with the in vivo confocal microscopy findings.

Posaconazole Treatment for Apophysomyces elegans Rhino-Orbital Zygomycosis following Trauma for a Male with Well-Controlled Diabetes

We report a case of rhino-orbital zygomycosis in a 43-year-old male with well-controlled diabetes mellitus. The patient initially received liposomal amphotericin B, but the infection continued to progress, so posaconazole treatment was begun and eventually led to the cure of his infection. The causative agent was identified as Apophysomyces elegans, an emerging cause of zygomycosis in immunocompetent hosts.

Histomorphometric study of placental villi vascular volume in toxemia and diabetes

The quantitative changes in the vascular tree in placentas from pregnancies complicated by diabetes mellitus and preeclampsia (PE) are not well defined. The purpose of this study was to quantify placental villi cross-sectional area of capillaries assessed by a computerized morphometry system in pregnancies complicated by PE (n = 23), well-controlled pregestational diabetes mellitus (PGDM; n = 10), and healthy controls (n = 13). Our aims were to test whether villous capillarization volume was changed in PE without intrauterine growth restriction or PGDM compared with the control group and to study these effects in 3 different areas of the placenta. Examination of placentas in women with PGDM and PE revealed limited pathological changes on light microscopic examination. However, the morphometric analysis revealed a more than 5-fold decrease of villous vascular volume in PGDM compared with controls (P = .003) and a 1.6-fold decrease in the PE group that did not reach statistical significance. These findings show quantitative changes in the villous vascular tree in PGDM that are not detectable by conventional light microscopy and suggest that morphometric analysis of the capillary tree may have diagnostic importance in this entity. The findings differ significantly from those previously reported in pregestational diabetes and do not differ significantly from those reported in PE without intrauterine growth restriction.

Continuous Glucose Monitoring in Diabetic Long Distance Runners

Marathon running is growing in popularity, and many diabetic patients are participating in various marathon races all over the world each year. This study aimed to investigate the prevalence and extent of glycemic excursions (hypo- and hyperglycemic) during a marathon run in patients with well-controlled diabetes mellitus using a continuous glucose monitoring system (CGMS). Five subjects with type 1 and one patient with type 2 diabetes mellitus were monitored with the Medtronic MiniMed CGMS during the 2002 Vienna City Marathon (n = 3) or the "Fernwärme run" (n = 3) long distance runs of 42.19/15.8 km. All six patients finished their course. The CGSM system was well tolerated in all patients over an average duration of 34 +/- 4.0 hours and it did not limit the patients' activities. The mean running time for the Vienna city marathon was 257 +/- 8 min (247 to 274 min) and for the Fernwärme run 134 +/- 118 min (113 to 150 min). A total of 1470 blood glucose measurements (mean 245 readings per subject) were performed. During and after the marathons frequent hypo- and hyperglycemic episodes with and without clinical symptoms were measured. Our data confirm that the CGMS may help to identify asymptomatic hypoglycemia or hyperglycemia during and after a long distance run. The system may also be helpful to improve our understanding about the individual changes of glucose during and after a marathon and may protect hypoglycemic or hyperglycemic periods in future races.

Pulsatility Index of Temporal and Renal Arteries as an Early Finding of Arteriopathy in Diabetic Patients

The objective of this study was to investigate the relationship between alterations in the elasticity of the temporal and the renal arteries and the grade of arteriopathy, using the pulsatility index in type II diabetic patients and healthy volunteers. All individuals were divided into groups. Group A consisted of 15 patients without risk factors (hyperlipidemia, hypertension, obesity, and smoking) and had well-controlled diabetes mellitus as demonstrated by normal values of HbA1c. Group B had 20 patients with two risk factors (hyperlipidemia and hypertension) and normal HbA1c. Group C (25 patients) had four risk factors and high values of HbA1c, and group D consisted of 20 healthy individuals. All patients were examined by use of color Doppler ultrasonography. Pulsatility index values were measured in the temporal and renal arteries. Pulsatility indices of temporal arteries were higher in group C than in groups A and B, whereas for the renal arteries, no significant difference was detected between the four groups. In our study there seems to be strong correlation between increased values of pulsatility index, mainly in the temporal arteries, and grade of arteriopathy in type II diabetic patients.

Glycemic control, oxidative stress, and lipid profile in children with type 1 diabetes mellitus

Background In diabetes mellitus, persistence of hyperglycemia was reported to cause increased production of oxidative parameters including malondialdehyde (MDA). In the present study, the effect of glycemic control on oxidative stress and the lipid profile of pediatric type 1 diabetes mellitus (DM) patients were investigated. Methods Serum total cholesterol, HDL cholesterol, VLDL cholesterol, apolipoprotein A, apolipoprotein B, lipoprotein a, HbA 1c, and MDA levels were assessed in 96 children with type 1 DM. Study cases were evaluated in two groups in view of their mean HbA 1c values, as metabolically well controlled (HbA 1c ≤8%) and poorly controlled (HbA 1c >8%) patients with DM. Fifty healthy children were included as normal controls. Results Total cholesterol, LDL cholesterol, apolipoprotein A, apolipoprotein B, and MDA levels of total diabetic patients were significantly ( p<0.05) higher than those of the control group. Serum MDA levels and MDA/LDL cholesterol index were significantly increased in metabolically poorly controlled in relation to metabolically well-controlled DM patients and were similar in metabolically well-controlled DM patients with relation to control group and in metabolically poorly controlled patients with relation to control group. Conclusions In the present study, increased levels of MDA, MDA/LDL index, and dyslipoproteinemia showed that especially metabolically poorly controlled DM children are at high risk of atherosclerosis and vascular complications of DM and that there is a significant relationship between the lipid profile and oxidative stress. Thus, it may be appropriate to evaluate MDA in addition to routine laboratory assessments in evaluation of type 1 DM pediatric patients.

Adiponectin concentrations as a criterion of metabolic control in persons with type 2 diabetes mellitus?

Adiponectin (ADP) is an adipocytokin with many antiatherogenic properties; its decreased level is associated with numerous atherogenic diseases and syndromes (e.g. diabetes mellitus (DM), dyslipidemia, endothelial dysfunction, hypertension, and obesity). Decreased ADP values in blood may be an independent risk factor of atherosclerotic (ATS) complications. 1) Do persons with type 2 diabetes have lower ADP values than individuals without DM but with a high risk of ATS complications? 2) Do ADP values differ between persons with well controlled and persons with uncontrolled type 2 diabetes? We examined 109 patients of the Metabolic Center of Hospital Sternberk. Out of them, 58 had type 2 diabetes, others were individuals with variously expressed risk factors of early atherosclerosis (obesity, hypertension, age, family history, smoking, dyslipidemia, etc.). In all persons under this study the following parameters were determined in peripheral venous blood: adiponectin, resistin, leptin, ObRe, cholesterol, HDL-cholesterol, triacylglycerols, glucose, HbA1c, creatinine, urea, ALT, AST, CRP, homocysteine, thrombocyte aggregation after CPG induction. The whole group was divided according to the presence of type 2DM into two subgroups; persons with diabetes were divided into the well controlled and uncontrolled subgroups. All data obtained were processed statistically using the software SPSS for Windows and Medcalc. The adiponectin/BMI index correlated negatively with HbA1c value (correlation coefficient -0.37, p = 0.00053), triacylglycerols (-0.4, p = 0.000001), P-glucose (-0.3, p = 0.0017), uricemia (-0.35, p = 0.0007) and positively with HDL-cholesterol value (0.6, p=0.00001). Women had higher adiponectin values than men. Persons with hypertension and with diabetes mellitus, individuals with atherogenic lipotype or persons with inflammation signs had lower values than individuals without these diseases and syndromes. Persons with wellcontrolled diabetes mellitus had higher values than persons with uncontrolled diabetes (medians of the adiponectin/BMI index 9.7 vs. 6.7, p < 0.01). Persons with type 2 diabetes mellitus have lower ADP values than persons with a high ATS risk without diabetes mellitus. Persons with wellcontrolled diabetes mellitus (DM) and with satisfactory compensation have significantly higher ADP levels (independently of other metabolic parameters of DM control). ADP may be a new marker of metabolic control in persons with a high risk of atherosclerotic complications.

Late corneal perforation after photorefractive keratectomy associated with topical diclofenac: Involvement of matrix metalloproteinases

Objective To report a case of a 50-year-old man who was initially seen with a corneal perforation in his right eye 2 months after a photorefractive keratectomy (PRK) procedure and to discuss the roles of topical diclofenac and matrix metalloproteinases (MMPs). Design Case report with tissue analysis. Main outcome measures Ocular examination, diagnostic workup, surgical treatment, and histologic, immunofluorescent, zymography, and real time-polymerase chain reaction studies on corneal button. Results Slit-lamp examination of the right eye revealed a 4-mm diameter area of central corneal thinning with a 2-mm diameter perforation at its center. Predisposing factors included prolonged postoperative topical diclofenac therapy for more than 2 months and a 10-year history of well-controlled diabetes mellitus. An extensive diagnostic workup ruled out a systemic autoimmune disease. A penetrating keratoplasty was performed. Results of immunohistochemical studies of the corneal button showed stromal accumulation of temporary type III and IV collagens, MMP-3, and MMP-9 in the anterior wounded stroma and MMP-9 in the basal corneal epithelial cells of the leading edge. Differential activity and expression of MMP-2 and MMP-9 were found between the central and peripheral corneal buttons. Conclusions Prolonged use of diclofenac and diabetes mellitus might be responsible for the corneal perforation after PRK in our patient. MMP-9 and MMP-3 might be involved in delayed wound closure and corneal melting.

Increased levels of asymmetric dimethylarginine in populations at risk for atherosclerotic disease. Effects of pravastatin

The aim of the present study was to investigate plasma levels of asymmetric dimethylarginine (ADMA), an important endogenous inhibitor of nitric oxide synthase, in populations at high risk for atherosclerosis as compared to healthy controls, and furthermore to evaluate the effect of cholesterol lowering therapy in individuals with hypercholesterolemia. The present study consisted of 32 men with untreated hypercholesterolemia (HC group), 38 individuals with well-controlled insulin-dependent diabetes mellitus (DM group) and 20 healthy individuals (controls). The HC subjects were randomly allocated into a double blinded, placebo-controlled cross-over designed study with 8 weeks treatment with pravastatin (40 mg/day) or matching placebo. ADMA levels were statistically significantly higher in DM and HC individuals as compared to controls ( P<0.001 for both), and the l-arginine/ADMA ratios were significantly lower in both groups ( P<0.001 and P<0.005, respectively). Significant reductions in total cholesterol (TC) and LDL-C levels on pravastatin were obtained ( P<0.001 for both), whereas no changes were observed in the levels of ADMA or the l-arginine/ADMA ratios. Statistically significant correlations between ADMA and TC and LDL-C were found ( r=0.41, P<0.001 for both). In conclusion, significantly elevated ADMA levels and reduced l-arginine/ADMA ratios were found in individuals with diabetes type-1 as well as in hypercholesterolemia. Treatment with pravastatin 40 mg/day for 8 weeks had no effect on the levels of ADMA in hypercholesterolemic men.

Reactive oxygen species generation by leukocytes in populations at risk for atherosclerotic disease

The aim of this study was to investigate intracellular levels of reactive oxygen species (ROS) in circulating leukocytes in populations at risk for atherosclerosis compared with in healthy individuals. The study populations consisted of 27 non-diabetic men (aged 40 - 69 years) with untreated hypercholesterolemia (HC), 13 individuals (aged 39 - 56 years) with well-controlled insulin-dependent diabetes mellitus (DM), and 20 healthy individuals (aged 26 - 61 years) (REF). Citrated whole blood was collected in fasting condition. Using flow cytometric techniques, the resting levels and the response upon phorbol 12-myristate 13-acetate (PMA, 100 ng/mL) stimulation of ROS were measured in circulating monocytes (MO) and granulocytes (GR). The relative mean fluorescence intensity (rMFI) in 10 4 leukocytes of fluorochromes mainly reflecting the levels of peroxynitrite (ONOO - ) hydrogen peroxide (H 2 O 2 ) and superoxide anion (O 2 - ) was recorded. Significantly, higher basal levels of ONOO - in GR from the combined risk population compared with REF were found (1.4 vs. 1.5 rMFI, p<0.05). Upon PMA stimulation, significantly lower levels of O 2 - in GR in the risk populations compared to REF (119 vs. 90 Si, p<0.001) were observed. In conclusion, increased resting levels of ROS in circulating granulocytes, but reduced response to PMA stimulation could be demonstrated in populations at risk for atherosclerosis compared with in healthy individuals. This might indicate a higher degree of resting oxidative reactions, with partly exhausted cells and less capacity to host defence.

Fatal Hypertrophic Cardiomyopathy in the Fetus of a Woman With Diabetes

In Brief BACKGROUND Hypertrophic cardiomyopathy is recognized in infants of diabetic mothers, and when it occurs it is generally benign and transient. We describe a case of fetal cardiac death caused by hypertrophic cardiomyopathy in an infant of a diabetic mother. CASE Hydrops fetalis caused by hypertrophic cardiomyopathy resulted in the death of a macrosomic male fetus of a young woman who had well-controlled diabetes mellitus and was treated with insulin therapy during pregnancy. CONCLUSION It is important to monitor fetal heart function in macrosomic infants of diabetic mothers. Hypertrophic cardiomyopathy might explain otherwise unexplained fetal deaths in women with diabetes. Fatal hydrops fetalis was associated with hypertrophic cardiomyopathy in the fetus of a woman with diabetes.

Fatal hypertrophic cardiomyopathy in the fetus of a woman with diabetes

BACKGROUND: Hypertrophic cardiomyopathy is recognized in infants of diabetic mothers, and when it occurs it is generally benign and transient. We describe a case of fetal cardiac death caused by hypertrophic cardiomyopathy in an infant of a diabetic mother. CASE: Hydrops fetalis caused by hypertrophic cardiomyopathy resulted in the death of a macrosomic male fetus of a young woman who had well-controlled diabetes mellitus and was treated with insulin therapy during pregnancy. CONCLUSION: It is important to monitor fetal heart function in macrosomic infants of diabetic mothers. Hypertrophic cardiomyopathy might explain otherwise unexplained fetal deaths in women with diabetes.

Profound changes in the GH-IGF-I system in adolescent girls with IDDM: can IGFBP1 be used to reflect overall glucose regulation?

Disturbances in the relations between insulin, growth hormone (GH) and insulin-like growth factor I (IGF-I) may be a major cause behind deteriorated metabolic control in adolescent girls with type I diabetes. These patients have increased GH secretion and low IGF-I concentrations. The aim of this study was to identify possible endocrine mechanisms behind good and poor glycaemic control in such girls, focusing on the insulin-GH-IGF-I axis. Ten girls with well-controlled insulin-dependent diabetes mellitus (IDDM), hemoglobin A1c (HbA1c) 6.5+/-0.4% (normal range 3.9-5.2%) and nine healthy controls were investigated and compared with 11 girls with poor glucose regulation, HbA1c 10.9+/-0.4%, and their corresponding controls. Serum profiles of glucose, insulin, GH and IGF-binding protein 1 (IGFBP1) were analysed in addition to IGF-I and HbA1c. Two interesting observations were made. GH concentrations were equally elevated in the two diabetic groups regardless of metabolic control (mean 24 h GH - girls with poorly controlled diabetes 10.0+/-1.0 mU/L vs 9.8+/-1.7 - girls with well-controlled diabetes; p=ns). Likewise, the IGF-I concentrations were reduced to the same extent (233+/-19 vs 242+/-23 microg/L; p=0.75). Secondly, despite similar insulin concentrations (mean 24 h insulin - girls with poorly controlled diabetes 22.9+/-2.6 and girls with well-controlled diabetes 27.3+/-2.9 mU/L, respectively; p=0.26), there was a marked difference in IGFBP1 concentrations between the two groups with IDDM (mean IGFBP1 - girls with poorly controlled diabetes 70.5+/-9.1 microg/L vs girls with well-controlled diabetes 28.6+/-3.3; p<0.001). Despite equally elevated GH concentrations that may induce insulin resistance, the markedly lower concentrations of IGFBP1 in the well-controlled group indicate a higher hepatic insulin sensitivity in these girls compared with those with a poor control. Furthermore, in spite of similar total IGF-I concentrations, the lower IGFBP1 concentrations may result in higher IGF-I bioactivity in the well-controlled group. This may be reflected in better growth of the well-controlled group whose height of 168.7+/-0.9 vs 163.6+/-1.2 cm was significantly different (p<0.004). IGFBP1 may be a marker of overall insulinization in adolescents with type 1 diabetes, independent of the absolute insulin dose used for therapy.

Stereological comparison of 3D spatial relationships involving villi and intervillous pores in human placentas from control and diabetic pregnancies.

In human placenta, 3D spatial relationships between villi and the maternal vascular bed determine intervillous porosity and this, in turn, influences haemodynamics and transport. Recently-developed stereological methods were applied in order to examine and quantify these relationships. Placentas were collected after 37 wk from control pregnancies and those associated with maternal diabetes mellitus classified according to duration and severity (White classification scheme). Two principal questions were addressed: (1) are normal spatial arrangements maintained in well-controlled diabetes mellitus? and (2) do arrangements vary between diabetic groups? To answer these questions, tissue sections cut at random positions and orientations were generated by systematic sampling procedures. Volume densities of villi (terminal + intermediate), intervillous spaces and perivillous fibrin-type fibrinoid deposits were estimated by test point counting and converted to global volumes after multiplying by placental volumes. Design-based estimates of the sizes (volume- and surface-weighted volumes) of intervillous 'pores' were obtained by measuring the lengths of point- and intersection-sampled intercepts. From these, theoretical numbers of pores were calculated. Model-based estimates (cylinder model) of the hydraulic diameters and lengths of pores were also made. Second-order stereology was used to examine spatial relationships within and between villi and pores and to test whether pair correlation functions deviated from the value expected for 'random' arrangements. Estimated quantities did not differ significantly between diabetic groups but did display some departures from control values in non-insulin-dependent (type 2) diabetic placentas. These findings support earlier studies which indicate that essentially normal microscopical morphology is preserved in placentas from diabetic subjects with good glycaemic control. Therefore, it is likely that fetal hypoxia associated with maternal diabetes mellitus is due to metabolic disturbances rather than abnormalities in the quantities or arrangements of maternal vascular spaces.

Prevalence of pituitary tumors among diabetic cats with insulin resistance.

To determine prevalence of pituitary tumors, detectable by means of computed tomography or magnetic resonance imaging, in cats with insulin resistance suspected to have acromegaly or hyperadrenocorticism versus cats with well-controlled diabetes mellitus. Case series. 16 cats with insulin resistance that were also suspected to have acromegaly (n = 12) or pituitary-dependent hyperadrenocorticism (4) and 8 cats with well-controlled diabetes mellitus. Computed tomography was performed on all 16 cats with insulin resistance and 2 cats in which diabetes mellitus was well-controlled. The remaining 6 cats in which diabetes mellitus was well-controlled underwent magnetic resonance imaging. Images were obtained before and immediately after i.v. administration of contrast medium. Computed tomography revealed a mass in the region of the pituitary gland in all 16 cats with insulin resistance. Maximum width of the masses ranged from 4.4 to 12.7 mm; maximum height ranged from 3.1 to 12.6 mm. Results of computed tomography performed on 2 cats with well-controlled diabetes and magnetic resonance imaging performed on the remaining 6 cats were considered normal. Results suggest that cats with insulin resistance suspected to have acromegaly or pituitary-dependent hyperadrenocorticism are likely to have a pituitary mass detectable by means of computed tomography or magnetic resonance imaging.

Periodontal management of the patient with diabetes mellitus.

Diabetes mellitus is a common medical disorder that will be encountered by every practicing dentist. Knowledge by the dentist of the general and oral signs and symptoms of undiagnosed or poorly controlled diabetes mellitus are essential, and patients displaying these signs or symptoms should receive medical referral. Patients suspected, or known to suffer from undiagnosed or uncontrolled diabetes mellitus should receive only emergency care until their health status has been properly evaluated. In the event the degree of control of a known diabetic is unknown or the patient is poorly controlled, antibiotic therapy should be administered in conjunction with any necessary surgical procedure or in the presence of oral infection. The practitioner must be prepared to manage diabetic emergencies should they occur in the dental office, and hypoglycemic incidents are most likely. The developing therapies now available for medical management of diabetes mellitus suggest that this condition will be more effectively controlled in the future, but medical consultation is important to proper periodontal patient management. New evidence suggests that advanced periodontal disease may interfere with diabetes mellitus control and the physician should be made aware of the patient's periodontal status. Under most circumstances, the well-controlled diabetes mellitus patient can receive safe and effective periodontal therapy with some modification of office protocol, and there is little reason to anticipate that the controlled diabetes mellitus patient cannot look forward to a lifetime of periodontal health if proper and timely periodontal therapy is rendered and the patient maintains effective oral hygiene measures accompanied by appropriate supportive periodontal recall therapy.

The human placenta in diabetes mellitus

The quantitative changes in the vascular tree in placentas from pregnancies complicated by diabetes mellitus and preeclampsia (PE) are not well defined. The purpose of this study was to quantify placental villi cross-sectional area of capillaries assessed by a computerized morphometry system in pregnancies complicated by PE (n = 23), well-controlled pregestational diabetes mellitus (PGDM; n = 10), and healthy controls (n = 13). Our aims were to test whether villous capillarization volume was changed in PE without intrauterine growth restriction or PGDM compared with the control group and to study these effects in 3 different areas of the placenta. Examination of placentas in women with PGDM and PE revealed limited pathological changes on light microscopic examination. However, the morphometric analysis revealed a more than 5-fold decrease of villous vascular volume in PGDM compared with controls (P = .003) and a 1.6-fold decrease in the PE group that did not reach statistical significance. These findings show quantitative changes in the villous vascular tree in PGDM that are not detectable by conventional light microscopy and suggest that morphometric analysis of the capillary tree may have diagnostic importance in this entity. The findings differ significantly from those previously reported in pregestational diabetes and do not differ significantly from those reported in PE without intrauterine growth restriction.

Quantitative studies on the villi, trophoblast and intervillous pores of placentae from women with well-controlled diabetes mellitus

Human placentae from well-controlled diabetic women were collected after 37 weeks of gestation and divided into three groups according to the duration and severity of diabetes mellitus established by White classification criteria. A fourth group of subjects served as matched controls. Various morphometric variables not estimated hitherto (including the star volumes of villous ‘domains’ and intervillous ‘pores’ and trophoblast surface denudation) were assessed stereologically. The aims were to test whether or not (1) control values of these structural quantities are preserved in well-controlled diabetes mellitus, and (2) differences occurred between alternative diabetic groups. Placental specimens were obtained by systematic random sampling procedures and paraffin sections were cut at random positions and orientations. Volume densities of peripheral (terminal+intermediate) villi and intervillous spaces were estimated by test point counting and multiplied by placental volumes in order to convert them into absolute volumes. Volume estimates were also obtained for trophoblast, syncytiotrophoblast nuclei and intervillous fibrin-type fibrinoid. Villous surface areas were estimated by intersection counting and the star volumes of villi and intervillous pores were obtained by measuring the lengths of point-sampled intercepts. Calculations were also made of the theoretical numbers of villous domains and intervillous pores and of the numbers of syncytiotrophoblast nuclei. No significant differences were detected between control and diabetic placentae, or between White classes, for any of the estimated quantities. It is concluded that normal values are preserved by good glycaemic control regardless of diabetic grouping.

Aerobic circuit exercise training: Effect on adolescents with well-controlled insulin-dependent diabetes mellitus

Objectives: To test the safety and effects of exercise conditioning on cardiorespiratory fitness, body composition, muscle strength, glucose regulation, and lipid/cholesterol levels. Subjects: Ten male adolescents with insulin-dependent diabetes mellitus (IDDM) and 10 adolescent nondiabetic (ND) subjects. Design: Pretest, posttest intervention trial with control group. Setting: University-based human performance laboratory. Intervention: Mixed endurance and calisthenic/strength activities performed at a rapid pace three times weekly for 12 weeks. Results: Only one subject with IDDM experienced hypoglycemia after a single exercise session. Both subject groups improved their cardiorespiratory endurance ( p < .05). Lean body mass of IDDM subjects increased by 3.5% ( p < .05). Subjects with and without IDDM lowered their percent body fat ( p < .05 and .001, respectively). Strength improvement of IDDM subjects ranged from 13.7% ( p < .001) to 44.4% ( p < .01), depending upon the maneuver. Fasting blood plasma glucose for all subjects was unchanged by training, but glycosylated hemoglobin A 1c of IDDM subjects was reduced by .96 percentage point ( p < .05). Reductions of HbA 1c benefitted subjects exhibiting poor preconditioning glycemic control. Low-density lipoprotein cholesterol was decreased in subjects with IDDM ( p < .05), but not total cholesterol or triglycerides. Conclusion: Adolescents with IDDM undergoing aerobic circuit training improve their cardiorespiratory endurance, muscle strength, lipid profile, and glucose regulation. Aerobic circuit training is safe for properly trained and monitored adolescent diabetics.

Population pharmacokinetics of glyburide in patients with well-controlled diabetes.

To investigate glyburide pharmacokinetics in patients with well-controlled noninsulin-dependent diabetes mellitus (NIDDM), and test the hypothesis that intersubject variability in the glyburide dose is due to patient differences in the drug's pharmacokinetics. Prospective, open-label study. University-affiliated, internal medicine outpatient clinic. Fifty-one patients with NIDDM (11 women, 40 men, mean age 56.7 +/- 15.3 yrs) receiving oral glyburide and with well-controlled glycohemoglobin levels 10.0% or below. After fasting overnight, patients ingested their regular morning dose of glyburide and then ate breakfast. Blood samples were drawn before dosing and between 0.5-2 hours, 2-5 hours, and 5-10 hours after dosing. Serum glyburide was assayed by high-performance liquid chromatography and pharmacokinetics by NONMEM. Glyburide clearance was proportional to weight and greater in older patients (> 60 yrs). Variability in the glyburide dose was not primarily due to intersubject differences in the drug's pharmacokinetics.