Diagnostic performance of HbA1c for diabetes in Arab vs. European populations: a systematic review and meta-analysis.

AIM: To examine differences in the performance of HbA1c for diagnosing diabetes in Arabs compared with Europeans. METHODS: The PubMed, Embase and Cochrane library databases were searched for records published between 1998 and 2015. Estimates of sensitivity, specificity and log diagnostic odds ratios for an HbA1c cut-point of 48 mmol/mol (6.5%) were compared between Arabs and Europeans, using a bivariate linear mixed-model approach. For studies reporting multiple cut-points, population-specific summary receiver operating characteristic (SROC) curves were constructed. In addition, sensitivity, specificity and Youden Index were estimated for strata defined by HbA1c cut-point and population type. Database searches yielded 1912 unique records; 618 full-text articles were reviewed. Fourteen studies met the inclusion criteria; hand-searching yielded three additional eligible studies. Three Arab (N = 2880) and 16 European populations (N = 49 127) were included in the analysis. RESULTS: Summary sensitivity and specificity for a HbA1c cut-point of 48 mmol/mol (6.5%) in both populations were 42% (33-51%), and 97% (95-98%). There was no difference in area under SROC curves between Arab and European populations (0.844 vs. 0.847; P = 0.867), suggesting no difference in HbA1c diagnostic accuracy between populations. Multiple cut-point summary estimates stratified by population suggest that Arabs have lower sensitivity and higher specificity at a HbA1c cut-point of 44 mmol/mol (6.2%) compared with European populations. Estimates also suggest similar test performance at cut-points of 44 mmol/mol (6.2%) and 48 mmol/mol (6.5%) for Arabs. CONCLUSIONS: Given the low sensitivity of HbA1c in the high-risk Arab American population, we recommend a combination of glucose-based and HbA1c testing to ensure an accurate and timely diagnosis of diabetes.

Short-term comparison of once- versus twice-daily administration of glimepiride in patients with non-insulin-dependent diabetes mellitus.

OBJECTIVE: To investigate the metabolic effects and frequency of adverse events with 6 mg of glimepiride, a new oral sulfonylurea, given both in once- and twice-daily dosages to patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: This 15-week study involved 161 subjects with NIDDM. Subjects were randomized into two groups. For 4 weeks, group 1 received glimepiride 3 mg twice daily, and group 2 received glimepiride 6 mg once daily. After a 3-week placebo-washout period, twice- and once-daily regimens were crossed over for a second 4-week treatment period. Subjects were hospitalized at the end of each placebo or active-treatment phase. Their glucose concentrations were recorded at 20 time points over a 24-hour period, and their insulin and C-peptide concentrations were recorded at 16 time points over the same period. Parameters that were calculated included fasting, 24-hour, and postprandial concentrations of glucose, insulin, and C-peptide. RESULTS: One hundred six patients were randomized to receive treatment; 94 completed the entire study. Existing physiologic mechanisms of glucose control were apparently unimpaired by glimepiride treatment. Insulin concentrations increased more during the postprandial glucose peaks than when subjects were fasting. Both twice- and once-daily regimens proved equally effective in reducing concentrations of fasting, postbreakfast, postlunch, and postdinner plasma glucose. Twenty-four-hour mean glucose concentrations showed a slightly greater decrease from baseline for the twice-daily regimen; the difference between the regimens was statistically significant but not clinically meaningful. The incidence of adverse events with glimepiride approximated that obtained with placebo, with both groups reporting only one adverse event, headache, in more than 5% of the subjects. CONCLUSIONS: Glimepiride is equally effective whether administered once or twice daily. Glimepiride seems to stimulate insulin production primarily after meals, when plasma glucose concentrations are highest, but controls blood glucose throughout the day.

The influence of multiple dosing and age on the pharmacokinetics and pharmacodynamics of glipizide in patients with type II diabetes mellitus.

STUDY OBJECTIVES: To determine the pharmacokinetics and pharmacodynamics of glipizide after a single dose and 12 weeks of dosing in patients with type II diabetes mellitus, and evaluate the influence of aging. DESIGN: Comparison of single and multiple doses of glipizide. SETTING: University-affiliated outpatient internal medicine clinic and diabetes care unit. PATIENTS: Twenty patients (11 men, 9 women, mean age 55.2 +/- 9.9 yrs) with type II diabetes mellitus who were currently receiving oral hypoglycemic agents or were hyperglycemic with diet. INTERVENTIONS: A 24-hour pharmacokinetic evaluation of glipizide was assessed after a 5-mg dose at the start of therapy and after 12 weeks of therapy. Pharmacokinetic parameters were assessed using compartmental population analysis techniques. Glipizide pharmacodynamic evaluation was assessed by serum glucose, insulin, and C-peptide responses during a 4-hour Sustacal tolerance test performed at baseline before instituting glipizide therapy, with the first 5-mg dose, and at week 12 of therapy. Glipizide dosages were titrated to a targeted goal of fasting plasma glucose of 7.8 mmol/L or less or to reach maximum daily doses of 40 mg. MEASUREMENTS AND MAIN RESULTS: No significant differences in time to peak concentration, apparent volumes of distribution for the central and peripheral compartments, apparent oral clearance from the central compartment, distributional clearance between the central and peripheral compartments, or terminal elimination half-life were observed with a single dose and long-term dosing. The mean +/- SD terminal elimination half-lives were 9.67 +/- 5.6 and 9.35 +/- 4.6 hours after a single dose and 12 weeks, respectively. Fasting plasma glucose concentrations decreased from 12.3 +/- 3.6 mmol/L before the first dose of glipizide to 9.2 +/- 1.7 mmol/L after 12 weeks of treatment. The values for area under the serum concentration-time curve from zero to 4 hours for glucose (AUC0-4.glucose) were significantly reduced at week 12 (baseline 49.8 +/- 15.6, week 12 37.8 +/- 9.8 mmol/L/hr). Glipizide provoked an increase in serum insulin and C-peptide concentrations (AUC0-4.insulin: baseline 698 +/- 327, single dose 954 +/- 461, long-term dosing 945 +/- 600 pmol/L/hr). No significant change in insulin response was observed between single and multiple doses. No age-related differences in the pharmacokinetic parameters or the pharmacodynamic responses of glipizide were observed. CONCLUSIONS: Long-term dosing and aging have little effect on the pharmacokinetic profile of glipizide. In addition, glipizide stimulates insulin secretion to a similar extent following glucose challenge after a single dose and long-term administration.

Pharmacokinetics and pharmacodynamics of glyburide in young and elderly patients with non-insulin-dependent diabetes mellitus.

OBJECTIVE: To determine the influence of age on the pharmacokinetics and pharmacodynamics of glyburide after acute and chronic dosing in young and elderly subjects with non-insulin-dependent diabetes mellitus. DESIGN: Ten elderly (mean age 69.3 +/- 3.1 y) and 10 younger (mean age 45.6 +/- 4.5 y) patients received a glucose challenge test at baseline, with a 2.5-mg dose of glyburide at week 0 (acute dose) and again at weeks 6 and 12 of chronic glyburide therapy. Glyburide doses were titrated to a maximum daily dosage of 20 mg to achieve a glucose concentration of 7.8 mmol/L or less. During 24-h pharmacokinetic determinations at weeks 0, 6, and 12, serial blood samples were obtained for glyburide determination with HPLC. Serial blood samples for glucose, insulin, and C-peptide determinations were obtained at baseline (week -1) and at weeks 0, 6, and 12. RESULTS: All pharmacokinetic parameters assessed for glyburide were statistically comparable between the two age groups with the exception of a shorter time to peak concentration in the elderly at weeks 0 and 12. The glucose pharmacodynamic response to glyburide was not statistically different between the two groups. However, there was a statistically significant greater C-peptide response in the elderly group at all evaluation weeks. CONCLUSIONS: Aging appears to have no influence on the pharmacokinetics of glyburide. Observed pharmacodynamic differences indicate the necessity for dosage titration to a specified therapeutic response regardless of patient age.

Evaluation of a pharmaceutical care model on diabetes management.

OBJECTIVE: To assess the effectiveness of a pharmaceutical care model on the management of non-insulin-dependent diabetes mellitus (NIDDM) in urban African-American patients. DESIGN: Eligible patients were randomized to either a pharmacist intervention or control group and followed over a 4-month period. Patients in the intervention group received diabetes education, medication counseling, instructions on dietary regulation, exercise, and home blood glucose monitoring, and evaluation and adjustment of their hypoglycemic regimen. Patients in the control group continued to receive standard medical care provided by their physicians. SETTING: A university-affiliated internal medicine outpatient clinic. PARTICIPANTS: The study population consisted of urban African American patients with NIDDM currently attending the clinic. MAIN OUTCOME MEASURES: Primary outcome measures included fasting plasma glucose and glycated hemoglobin concentrations. Secondary outcome endpoints included blood pressure, serum creatinine, creatinine clearance, microalbumin to creatinine ratio, total cholesterol, triglycerides, high-density lipoprotein, and low density lipoprotein concentrations. Quality-of-life assessments were performed in both groups at baseline and at the end of the study. RESULTS: Thirty-nine patients (17 intervention, 22 control) completed the study. The intervention group consisted of 12 women and 5 men with a mean +/- SD age of 59 +/- 12 years, total body weight (TBW) of 93 +/- 22 kg, body mass index (BMI) of 34 +/- 7 kg/m2, and duration of NIDDM 6.8 +/- 6.5 years. The control group consisted of 15 women and 7 men with a mean age of 65 +/- 12 years, TBW of 88 +/- 19 kg, BMI of 33 + 7 kg/m2, and a duration of NIDDM of 6.2 +/- 4.8 y. Significant improvement in glycated hemoglobin (p = 0.003) and fasting plasma glucose (p =0.015) was achieved in the intervention group. No change in glycemia was observed in the control subjects. Statistically significant differences in the final glycated hemoglobin (p = 0.003) and fasting plasma glucose (p = 0.022) concentrations were noted between groups. No significant changes in blood pressure control, lipid profile, renal function parameters, weight, or quality-of-life measures were noted within or between groups. CONCLUSIONS: Our data demonstrate the effectiveness of pharmaceutical care in the reduction of hyperglycemia associated with NIDDM in a group of urban African-American patients.

Metformin: an antihyperglycemic agent for treatment of type II diabetes.

OBJECTIVE: To review the comparative efficacy of metformin, sulfonylureas, and insulin in the treatment of patients with type II diabetes. DATA SOURCES: Articles were identified by a MEDLINE search of articles from 1966 to 1994, using the terms metformin, sulfonylurea, chlorpropamide, glipizide, glyburide, tolazamide, tolbutamide, and insulin, published in English, French, or German. Articles also were identified from bibliographies of pertinent articles. STUDY SELECTION: With the exception of articles dealing with the pharmacology of metformin, only randomized, active, controlled studies were selected for review. DATA EXTRACTION: Effects of metformin therapy on metabolic and cardiovascular risk factors were abstracted: weight, blood pressure, total and low-density lipoprotein cholesterol, triglycerides, fasting and postprandial glucose, and glycosylated hemoglobin. DATA SYNTHESIS: Metformin is an antihyperglycemic agent with a mean bioavailability of 50-60%. It is eliminated primarily by renal filtration and secretion and has a half-life of approximately 6 hours in patients with type II diabetes. Although the half-life of metformin is prolonged in patients with renal impairment, no specific dosage adjustments have been recommended. This agent has no effect in the absence of insulin. Metformin is as effective as the sulfonylureas in treating patients with type II diabetes and has a more prominent postprandial effect than the sulfonylureas or insulin. When combined with a sulfonylurea, metformin has been shown to exert antihyperglycemic effects in addition to the sulfonylurea with which it is combined. Metformin decreases absorption of vitamin B12 and folic acid, although reported cases of megaloblastic anemia are rare. Cimetidine decreases the elimination of metformin; therefore, the manufacturer reccommends a reduced metformin dosage when these agents are combined. The most frequently reported adverse effects of metformin are gastrointestinal in nature (diarrhea, nausea, abdominal pain, and metallic taste, in decreasing order). Metformin has been used in Canada, Great Britain, and the rest of Europe for more than 30 years and was approved for use in the US in December 1994. CONCLUSIONS: Three trials comprise the Food and Drug Administration approval database (one foreign). Metformin will be most useful in managing patients with poorly controlled postprandial hyperglycemia, as its postprandial effect is much greater than that of the sulfonylureas. In contrast, sulfonylureas or insulin are more effective for managing patients with poorly controlled fasting hyperglycemia. Metformin should be considered a first-line agent, particularly in obese or hyperlipidemic patients.

The effects of obesity on the pharmacokinetics and pharmacodynamics of glipizide in patients with non-insulin-dependent diabetes mellitus.

The pharmacokinetics and pharmacodynamics of glipizide were evaluated in 20 patients with non-insulin-dependent diabetes mellitus (NIDDM). The group consisted of 12 obese subjects (seven women, five men; mean +/- SD age, 53.5 +/- 8.5 years; total body weight (TBW), 95.5 +/- 17.2 kg; percentage > IBW (ideal body weight), 57.8 +/- 31.7%); and eight nonobese subjects (two women, six men; age, 57.8 +/- 11.7 years; TBW, 80.8 +/- 9.9 kg; percentage > IBW, 15.6 +/- 10.3%). After a 2-week antidiabetic drug-free period, patients were started on glipizide therapy for 12 weeks. Glipizide dosages were titrated to achieve specified therapeutic goals or a maximum daily dose of 40 mg. Glipizide pharmacokinetics were assessed by serum concentrations obtained during a 24-h pharmacokinetic evaluation performed after the first 5-mg dose (SD) and after 12 weeks of chronic therapy (CD). Glipizide pharmacodynamics were evaluated with serum glucose, insulin, and C-peptide responses to Sustacal tolerance test done at baseline, after SD, and after CD. No statistically significant differences in the SD pharmacokinetic parameters (Tmax = 3.1 +/- 1.2 vs. 2.8 +/- 1.6 h; Cmax = 332.5 +/- 92.5 vs. 420.8 +/- 142 g/L; area under the curve extrapolated to infinity (AUCI) = 2,598.3 +/- 1,148 vs. 3,138.9 +/- 1,847 g/h/L; oral clearance/bioavailability (CL/F), 2.3 +/- 1.0 vs. 2.0 +/- 1.0 L/h; volume of distribution/bioavailability (V/F), 19.5 +/- 4.4 vs. 17.2 +/- 4.3 L; t1/2 = 5.0 +/- 2.3 vs. 5.2 +/- 2.0 h) were observed between the obese and nonobese groups, respectively. The pharmacokinetic parameters assessed under CD conditions were also closely matched in the two groups. No differences in glucose responses to Sustacal challenge at baseline, SD, and CD (AUC0-->4.glucose:baseline, 52.3 +/- 18.0 vs. 44.9 +/- 9.8; SD, 50.4 +/- 20.9 vs. 36.1 +/- 11.0; CD, 37.8 +/- 10.7 vs. 36.6 +/- 8.5 mM/h) were noted between the obese and nonobese groups, respectively. However, glucose concentrations increased more and decreased to a smaller extent after SD in the obese as compared to nonobese subjects. Mean fasting serum insulin and C-peptide concentrations were not statistically different between the two groups. However, obese subjects exhibited higher fasting insulin (114.0 +/- 69 vs. 68.8 +/- 52 pM) at week 12 evaluation and C-peptide concentrations (0.83 +/- 0.2 vs. 0.63 +/- 0.2 nM) after SD as compared to the nonobese group. A smaller percentage increase in C peptide in response to Sustacal challenge was observed in the obese compared to the nonobese subjects (baseline, 60 +/- 25 vs. 117 +/- 117; SD, 119 +/- 39 vs. 193 +/- 149; and CD, 97 +/- 56 vs. 163 +/- 67%). In summary, the influence of obesity on glipizide pharmacokinetics appeared to be of little clinical significance. The observed differences in pharmacodynamics require further evaluation.

Peripheral diabetic neuropathy: current concepts in treatment.

OBJECTIVE: To review pathophysiology and current concepts in the treatment of diabetic peripheral neuropathy (PN). DATA SOURCES: References were identified through a MEDLINE search of the English-language literature from 1976 through 1994. Additional references were obtained from reference lists of articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Clinical trials that involved an adequate number of patients and review articles were selected. Information from articles that was judged by the authors to be significant was selected for discussion. DATA SYNTHESIS: PN affects 5-50% of people with diabetes in the US and most commonly is characterized by tingling or burning sensations, particularly in the calves, ankles, and feet, with a loss of vibratory sense. Treatment of PN, for the most part, has been unsatisfactory. Therapy has been directed toward either improving nerve function or alleviating symptoms of PN, including pain and paresthesia. Glycemic control may slow the progression of PN. Hyperglycemia also is associated with decreased pain threshold in patients with diabetes mellitus. The aldose reductase inhibitors, particularly tolrestat, have been shown to improve objective and subjective neurologic function. Pain or paresthesia has been treated effectively with antidepressants, lidocaine, mexiletine, and capsaicin. The anticonvulsants phenytoin and carbamazepine may be effective, but are associated with a greater degree of adverse effects. Experimental treatments, such as gamma-linolenic acid, gangliosides, uridine, and the corticotropin4-9 analog ORG 2766, have been effective in improving neurologic function. CONCLUSIONS: Treatment of PN remains unsatisfactory. Therapy should be directed toward prevention with glycemic control and symptomatic treatment of existing PN.

Diabetes and related metabolic risk factors among Arab Americans.

OBJECTIVE: To estimate the incidence of noninsulin-dependent diabetes mellitus (NIDDM) and associated metabolic abnormalities such as impaired glucose tolerance, increased blood pressure, hyperinsulinemia, and obesity in the Arab-American community in the Detroit metropolitan area. METHODS: Subjects were selected randomly from a computer-generated list provided by the Arab-American Center for Economic and Social Services. Laboratory studies included a 2-hour, 75-g oral glucose tolerance test with glucose, insulin, and C-peptide determinations. RESULTS: Of the 105 volunteers studied, 57 were women and 48 were men. Mean +/- SD age was 46.0 +/- 13.0 years. Body mass index was 30.4 +/- 6.8 kg/m2, with 68% of subjects having a body mass index of 27 kg/m2 or more. Of the study participants, 33% had NIDDM, 8.6% had impaired glucose tolerance, and 58% had normal glucose tolerance. Subjects with diabetes, compared with subjects who had normal glucose tolerance, exhibited increased fasting insulin (98 +/- 69 vs 55 +/- 31 pmol/L; p = 0.00056); higher cholesterol (6.03 +/- 1.03 vs 5.09 +/- 1.22 mmol/L; p = 0.00073); marginally lower high-density lipoprotein cholesterol (0.98 +/- 0.21 vs 1.14 +/- 0.31 mmol/L; p = 0.054); higher triglycerides (7.84 +/- 5.79 vs 3.83 +/- 2.15 mmol/L; p = 0.00002); and higher diastolic (83.7 +/- 8.9 vs 78.3 +/- 8.0 mm Hg; p = 0.014) as well as systolic (132.5 +/- 16.0 vs 119.0 +/- 10.6 mm Hg; p = 0.00001) blood pressures CONCLUSIONS: This pilot study demonstrates that diabetes may be a frequent medical problem in the Arab-American community. A well-designed epidemiologic study is warranted to validate these results and to elucidate the underlying mechanisms responsible for these findings.

Comparison of pharmacokinetics and pharmacodynamics of short- and long-term glyburide therapy in NIDDM.

OBJECTIVE: To examine the pharmacokinetics and pharmacodynamics of glyburide after single- and multiple-dose administration in patients with type II diabetes. RESEARCH DESIGN AND METHODS: Twenty patients with type II diabetes between 40 and 70 years of age participated in the study. A 24-h pharmacokinetic evaluation including a 4-h Sustacal tolerance test was conducted before instituting glyburide therapy (baseline), after the first 2.5-mg test dose of glyburide and at weeks 6 and 12 of chronic glyburide therapy. Glyburide doses were titrated with a target goal of achieving a fasting plasma glucose of < or = 7.8 mmol/l or to reach maximum daily doses of 20 mg. RESULTS: A significant prolongation in the elimination half-life (t1/2: week 0, 4.0 +/- 1.9 h; week 6, 13.7 +/- 10.5 h; and week 12, 12.1 +/- 8.2 h) and an increased volume of distribution of glyburide was observed during chronic dosing. These results strongly suggest possible drug accumulation. No differences in pharmacokinetic parameters were noted between evaluations at week 6 or week 12. Changes in pharmacodynamic response of glucose, insulin, and C-peptide to chronic glyburide therapy were observed. Glyburide therapy significantly reduced plasma glucose levels at weeks 6 and 12 (percent changes in AUC0-->4. glucose from baseline: week 0, -3 +/- 11%; week 6, -29 +/- 13%; and week 12, -26 +/- 19%). Pancreatic insulin secretion was acutely enhanced and maintained during long-term therapy. Responsiveness to therapy as assessed by the ratio of AUC0-->4.glucose:AUC0-->4.C-peptide was significantly improved at all weeks compared with baseline. No pharmacodynamic response differences were observed between the week 6 and the week 12 evaluations. CONCLUSIONS: This study demonstrates that significant differences in glyburide pharmacokinetics and pharmacodynamics exist between single-dose and steady-state conditions. These differences support the need for careful dosage titration of glyburide to achieve a desired therapeutic response in patients with type II diabetes.

The effect of stress on glycemic control in patients with type II diabetes during glyburide and glipizide therapy.

Stress adversely affects glycemic control in patients with type II diabetes mellitus. In addition, stress reduction with relaxation techniques or medication use in the management of hyperglycemia has been recommended. This study examined the relationship of glycemic control to self-reported stress in 19 patients with type II diabetes mellitus who were randomly allocated to receive either glyburide or glipizide for 16 weeks in a double-blind crossover design. Each treatment phase was preceded by a 2-week washout period. A previously designed and validated nine-item stress questionnaire was used to assess areas such as safety, financial wellbeing, energy level, health, etc. These areas were evaluated as more/less, better/worse, or no change. The stress questionnaire, fasting blood glucose (FBG), and glycosylated hemoglobin (GHb) concentrations were completed or measured at the end of glyburide and glipizide treatment periods. By assigning a value of 1, 2, or 3 to a positive, no change, or negative response, respectively, a composite stress score was computed and compared with glycemic control as assessed by FBG and GHb. Regression analysis showed highly significant correlations (P < .05) between stress scores and FBG (r = .70) as well as GHb (r = 0.84) with glipizide therapy. No such correlation was noted with glyburide (FBG: r = 0.29; GHb: r = 0.29). These findings suggest that during glyburide treatment, in contrast to glipizide, an increase in stress was not associated with a corresponding rise in blood glucose or worsening of metabolic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-converting enzyme inhibitors in diabetic nephropathy.

OBJECTIVE: Diabetic nephropathy (DN) is a leading cause of kidney disease in the US. At least four factors influence whether people with diabetes will develop DN: (1) hypertension, (2) hyperglycemia, (3) dietary protein intake, and (4) intrarenal hemodynamics. The angiotensin-converting enzyme (ACE) inhibitors are known to affect blood pressure (BP) and intrarenal hemodynamics; thus, they may prevent the onset of DN or slow the decline in renal function once DN has been diagnosed. DATA SOURCES: English-language, controlled, and crossover studies published between 1973 and 1991 and indexed in MEDLINE under the headings diabetic nephropathies and angiotensin-converting enzyme inhibitors. MAIN OUTCOME MEASURES: The primary outcome indicators of interest were the effects of the ACE inhibitors captopril, enalapril, and lisinopril on BP control and urinary albumin excretion rate. CONCLUSIONS: ACE inhibitors delay the onset and slow the progression of DN in people with diabetes independent of BP effects. They also slow the progression of DN in people with diabetes who have poorly controlled hyperglycemia. The proper dose and time at which to initiate ACE inhibitor therapy to prevent the appearance of DN is not known. It is also not known how long the beneficial effects of ACE-inhibitor therapy persists as only two studies have followed patients for more than one year. Finally, large, long-term, controlled clinical trials are needed before ACE inhibitors can be considered for prophylactic use to prevent the onset and/or progression of DN.

The pharmacokinetics and pharmacodynamics of 12 weeks of glyburide therapy in obese diabetics.

We have studied the pharmacokinetics and pharmacodynamics of glyburide during long-term therapy in 20 patients with type II diabetes mellitus. The patients were divided according to body mass index (BMI) into an obese group [n = 12, age 55(13) y, BMI 36.2(9.2) kg.m-2, total body weight (TBW) 100(23) kg], and a non-obese group [n = 8, age 61(13) y, BMI 24.5(2.1) kg.m-2, TBW 73(7) kg]. The dosages of glyburide were titrated to achieve specified therapeutic goals based upon serum glucose concentrations or to a maximum dosage of 20 mg per day. The pharmacokinetics of glyburide were determined at week 12 of treatment. On the study day, the patients took a 2.5 mg liquid test dose of glyburide with a Sustacal meal challenge. The elimination rate constant (lambda z), clearance (CL), and apparent volume of distribution (Vz) were 0.08 h-1, 3.3 l.h-1, and 47.0 l in the obese group, and 0.07 h-1, 3.1 l.h-1, and 56.8 l in the non-obese group. These values were not statistically significantly different. However, there were differences between the groups when the volume and clearance were corrected by TBW or BMI but not by ideal body weight (IBW) or fat-free mass (FFM). Regression analysis between the pharmacokinetic variables and body weight status revealed statistically significant correlations between volume or clearance and body weight. However, due to large inter-patient variability, these relations were relatively weak and were considered to be non-predictive.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible correlation between glycemia and blood pressure in black, diabetic, hypertensive patients.

OBJECTIVE: To determine if there is any association between glycemia and blood pressure in black patients with hypertension and diabetes mellitus whose antihypertensive medications had been unchanged for six months. DESIGN: Retrospective, from March 1990 through February 1991. SETTING: Internal medicine ambulatory clinic at Detroit Receiving Hospital/University Health Center. PATIENTS: Patients seen during this period with hypertension and type II diabetes. Of the 639 possible subjects, 124 met the following criteria: (1) no change in antihypertensive medications for six months, (2) absence of secondary hypertension, and (3) weight change (if any) was less than five percent. Changes in antihypertensive medication(s) excluded 388 patients, secondary hypertension excluded 3, weight changes of more than five percent excluded 94, and lack of matching postprandial capillary blood glucose (PCBG) values excluded 30. The mean age of the subjects was 66.8 years, mean diabetes duration was 12.0 years, mean PCBG was 10.7 mmol, mean systolic blood pressure (SBP) was 1543 mm Hg, mean diastolic blood pressure (DBP) was 90.1 mm Hg. There were 28 men in the study and 96 women; 90 were obese (body mass index greater than 25 kg/m2) and 34 were nonobese. The diabetes was managed with insulin in 67 patients, with sulfonylureas in 50, and with diet in 7. INTERVENTION: None MAIN OUTCOME MEASURES: SBP and DBP versus PCBG at matching time both at baseline and at six months. RESULTS: There was a positive association between blood pressure measurements and glycemia. Overall change in SBP was strongly correlated with PCBG changes (r = 0.745, p less than 0.0001). Improved glycemia correlated with improved SBP control (r = 0.330, p less than 0.0024). Deterioration of glycemia correlated with a worsening of SBP control (r = 0.445, p less than 0.0053). The method of blood glucose control had no statistically significant effect (ANOVA) on these results. CONCLUSIONS: Glycemia is positively associated with blood pressure.

An evaluation of the therapeutic effects and dosage equivalence of glyburide and glipizide.

Nineteen noninsulin-dependent diabetic patients [ten women, nine men, aged 36-80 years (mean +/- SE 56.8 +/- 2.7 years)] were randomized to receive either glyburide or glipizide for 16 weeks, in a double-blind crossover fashion. A 2-week washout period preceded each treatment period. The patients measured blood glucose concentrations 16 times weekly using Chemstrip-bG. The medication dosages were titrated to achieve fasting blood glucose concentrations of less than or equal to 6.2 mM and preprandial and postprandial concentrations of less than or equal to 9.0 mM, or to a total daily dose of 20 mg for glyburide and 40 mg for glipizide. Glyburide therapy resulted in a significant decline in fasting, preprandial, postprandial and bedtime blood glucose levels, while glipizide treatment led to a significant lowering of postprandial and bedtime blood glucose. Furthermore, fasting, preprandial and postprandial blood glucose concentrations were significantly lower during glyburide as compared to glipizide treatment phase. Glycosylated hemoglobin levels were decreased only with glyburide. Serum C-peptide and insulin concentrations were not altered over the entire study. The mean final daily dose of glyburide (15.4 +/- 1.6 mg) was markedly lower than that of glipizide (29.7 +/- 3.1 mg). Thus, in this patient population, glyburide was twice as potent on a weight basis than glipizide.

Enoxacin: a new fluoroquinolone.

The chemistry, mechanisms of action and resistance, pharmacokinetics, antimicrobial spectrum, clinical efficacy, adverse effects, and drug interactions of enoxacin are reviewed. Enoxacin is a new fluoroquinolone compound structurally related to nalidixic acid. Its antimicrobial spectrum and activity are comparable to those of the fluoroquinolones norfloxacin and ciprofloxacin. It has a broad spectrum of activity against gram-negative and gram-positive microorganisms, but like the other fluoroquinolones it is less active against gram-positive micro-organisms. Anaerobic organisms are generally resistant to enoxacin. It is rapidly and nearly completely absorbed after oral administration and is distributed widely in body fluids and tissues. The drug is predominantly excreted via the kidney, with a relatively long serum elimination half-life of approximately five hours. Serum and urinary concentration of enoxacin exceed the minimum inhibitory concentrations for most gram-negative and many gram-positive pathogens. Clinical trials have shown enoxacin to be effective for the treatment of gonorrhea, cystitis, complicated urinary-tract infections, and skin and skin structure infections. There is some evidence that enoxacin may be useful for treatment of lower-respiratory-tract infections and ear, nose, and throat infections. The most commonly reported adverse effects are mild gastrointestinal and central nervous system symptoms. Concomitant enoxacin and theophylline therapy has been associated with toxic serum concentrations of theophylline. Interactions have also been reported with caffeine, antacids, cimetidine, warfarin, and fenbufen. Enoxacin (Comprecin, Parke-Davis/Warner-Lambert) will be available in 200-, 300-, and 400-mg tablets for oral administration. Enoxacin is usually taken twice daily. A single 400-mg dose is effective therapy for uncomplicated gonorrhea. Since enoxacin, ciprofloxacin, and norfloxacin have many similar properties, formulary decisions involving these agents should be based on the individual institution's need to treat certain types of infections and pathogenic organisms. Enoxacin has been shown to be an effective agent for the treatment of urinary-tract, genital-tract, and skin and soft-tissue infections, including those that currently require injectable antimicrobial agents or that are resistant to conventional therapy.

Glycosylated hemoglobin levels and self-reported stress in adults with diabetes.

This study examined the relationship between glycosylated hemoglobin and self-reported stress in a sample of adult Type II diabetics. The study sample was drawn from participants in a randomized clinical trial of the comparative effectiveness of two oral antihyperglycemic drugs in the treatment of non-insulin-dependent diabetes. The 19 study participants were asked to complete a brief questionnaire on recent stress. Stress scores were then compared with levels of glycosylated hemoglobin. Correlations between glycosylated hemoglobin and stress scores were highly significant, a finding of particular clinical relevance in view of the relatively small number of participants. These findings suggest that sustained stress may contribute to poor glucose control in diabetics. Individuals interested in stress-related research may find glycosylated hemoglobin a useful marker of physiological stress.

Oral methoxsalen photochemotherapy of extensive pityriasis alba. Preliminary report.

Six patients with extensive pityriasis alba were treated with oral methoxsalen, followed by exposure to midday summer sun or exposure to long-wave ultraviolet radiation in a psoralens plus ultraviolet A (PUVA) cabinet. Complete clearing or marked improvement was obtained in five patients in less than 4 weeks of treatment. The patient with the most extensive skin involvement and the longest duration of the disease achieved a marked degree of improvement after 15 weeks of therapy. A long-term follow-up is still required to define the maintenance treatment and its efficacy.