The metabolic syndrome in the West Bank population: an urban-rural comparison.

OBJECTIVE: To compare the prevalence of components of the metabolic syndrome, including hypertension, abnormal glucose metabolism, dyslipidemia, central obesity, and overall obesity, between a rural and an urban Palestinian West Bank community. RESEARCH DESIGN AND METHODS: A total of 500 rural and 492 urban men and women aged 30-65 years participated in a community-based cross-sectional survey Diabetes and impaired glucose tolerance were diagnosed using the oral glucose tolerance test. BMI, waist-to-hip ratio, and blood pressure were measured, and blood samples were taken from each subject. Sociodemographic characteristics were investigated using a questionnaire. RESULTS: Hypertriglyceridemia, low HDL cholesterol, overall obesity, and smoking were significantly more prevalent in the urban population, whereas central obesity was more prevalent in the rural population. Prevalence of hypertension was not significantly different between the rural and urban populations (25.4 and 21.5%, respectively; P = 0.15). The age-adjusted prevalences of diabetes were high: 11.3% (8.5-14.1 95% CI) and 13.9% (10.8-17.0) in the rural and urban populations, respectively, but not significantly different. In each community, the age-adjusted prevalence of the metabolic syndrome as defined by the World Health Organization was 17%. CONCLUSIONS: Although no significant differences were found in the prevalences of hypertension and diabetes between the two populations, other components of the metabolic syndrome, namely elevated triglycerides, low HDL cholesterol, and overall obesity, were more prevalent in the urban population. Given the rapid urbanization of the Palestinian population, the implications for a rise in noncommunicable diseases should be a major public health concern.

Type 2 diabetes and maternal family history: an impact beyond slow glucose removal rate and fasting hyperglycemia in low-risk individuals? Results from 22.5 years of follow-up of healthy nondiabetic men.

OBJECTIVE: Although an excess transmission of type 2 diabetes from mothers has been documented, whether this is an independent trait or whether the effect can be detected early through risk factors for type 2 diabetes remains to be elucidated. The objective of this study was to investigate the prevalence of and the possible prospective effect of family history on type 2 diabetes incidence adjusted for multiple diabetes risk factors in a 22.5-year follow-up study of healthy men. RESEARCH DESIGN AND METHODS: A total of 1,947 apparently healthy nondiabetic men with fasting blood glucose (FBG) levels <110 mg/dl at baseline, in whom an intravenous glucose tolerance test (IVGTT) was administered and several conventional risk factors were measured, were followed for 22.5 years. Family history data were obtained at the baseline examination, and morbidity data were obtained from repeated investigations, hospital records, and death certificates. RESULTS: A total of 131 men reported maternal diabetes family history only, 65 men reported paternal diabetes family history only and 10 men reported both maternal and paternal diabetes family history. Among the 1,947 men, 143 cases of type 2 diabetes developed during 22.5 years of observation. Maternal family history and combined maternal and paternal family history predisposed to future type 2 diabetes both in univariate Cox analysis and in multivariate Cox regression analysis after adjusting for glucose disappearance rate (Rd) during an IVGTT, FBG level, BMI, physical fitness, triglyceride level, and age. Maternal family history showed a relative risk (RR) of 2.51 (95% CI 1.55-4.07), combined maternal and paternal family history showed an RR of 3.96 (1.22-12.9), and paternal family history showed an RR of 1.41 (0.657-3.05) in multivariate analysis. CONCLUSIONS: Maternal family history appears to be an important risk factor for type 2 diabetes independent of prediabetic Rd, FBG, BMI, and physical fitness levels.

Fasting blood glucose: an underestimated risk factor for cardiovascular death. Results from a 22-year follow-up of healthy nondiabetic men.

OBJECTIVE: Because of the available conflicting epidemiological data, we investigated the possible impact of fasting blood glucose as a risk factor for cardiovascular death in nondiabetic men. This study reports the results from a 22-year prospective study on fasting blood glucose as a predictor of cardiovascular death. RESEARCH DESIGN AND METHODS: Of the 1,998 apparently healthy nondiabetic men (aged 40-59 years), a total of 1,973 with fasting blood glucose < 110 mg/dl were included in the study in which also a number of conventional risk factors were measured at baseline. RESULTS: After 22 years of follow-up, 483 men had died, 53% from cardiovascular diseases. After dividing men into quartiles of fasting blood glucose level, it was found that men in the highest glucose quartile (fasting blood glucose > 85 mg/dl) had a significantly higher mortality rate from cardiovascular diseases compared with those in the three lowest quartiles. Even after adjusting for age, smoking habits, serum lipids, blood pressure, forced expiratory volume in 1 s, and physical fitness (Cox model), the relative risk of cardiovascular death for men with fasting blood glucose > 85 mg/dl remained 1.4 (95% CI 1.04-1.8). Noncardiovascular deaths were unrelated to fasting blood glucose level. CONCLUSIONS: Fasting blood glucose values in the upper normal range appears to be an important independent predictor of cardiovascular death in nondiabetic apparently healthy middle-aged men.

Sandostatin LAR in acromegalic patients: long-term treatment.

We have evaluated the long term effects and safety of Sandostatin LAR, a long acting formulation of octreotide, during 18 subsequent injections given every fourth week to 14 octreotide-sensitive acromegalic patients. The dosages (20, 30, or 40 mg) were adjusted according to GH response, side-effects, or symptom relief and assessed on day 28 after each injection. We found a stable and consistent suppression of GH and insulin-like growth factor (IGF-I) during the entire study period. Daily mean GH levels were suppressed below 2 micrograms/L in 9, to between 2-5 micrograms/L in 3, and to between 5-10 micrograms/L in 2 patients. The corresponding IGF-I values were suppressed to below 500 micrograms/L in 9 patients and to between 500-1000 micrograms/L in the remaining 5 patients. Increasing the dosage of Sandostatin LAR from 20 to 30 mg had no obvious additional effect on GH suppression, but provided a further decrease in IGF-I levels. Forty milligrams of the drug had no additional effect on GH or IGF-I compared to 30 mg. Acromegalic signs and symptoms improved during treatment. Although the fluctuations of daily mean octreotide levels were high, dosage increments caused an increase in the average serum concentration in the individual patient. Pituitary tumor size reduction was seen in all previously untreated patients (n = 4). We found only minor changes in glucose metabolism (oral glucose tolerance test and hemoglobin A1C) during treatment, but no biologically relevant changes in thyroid function (TSH, T3, and free T4). One patient developed asymptomatic gallstones, and another acquired vitamin B12 deficiency during treatment. The drug is well tolerated during long term treatment. Sandostatin LAR may well be the future medical treatment of choice for acromegalic patients.

Sandostatin LAR in acromegalic patients: a dose-range study.

Sandostatin LAR is a sustained release formulation of octreotide that has been developed by microencapsulating the drug with biodegradable poly(lactide-glycolide)-glucose. We have investigated the efficacy and tolerability of Sandostatin LAR given as a single dose im to patients with active acromegaly who showed good GH suppression during a 2- to 4-week pretreatment period with octreotide given sc. Two double blind studies were performed. Initially, 14 patients were randomized and observed over 42 days after a single im injection of 3, 6, 9, or 12 mg Sandostatin LAR. In the second study, 15 patients were randomized and observed over 60 days after a single im injection of either 20 or 30 mg Sandostatin LAR. Assessments of 12-h GH and octreotide profiles and adverse events were made on day -14 (during treatment with Sandostatin, sc); day 0 (off treatment after wash-out period); days 1, 7, 14, 21, 28, 35, and 42; and, for study 2, also on days 49 and 60 after the im injection. Only injections of 20 or 30 mg were followed by a suppression of basal GH and insulin-like growth factor I to levels comparable to those seen during sc treatment. The suppression of mean GH to less than 5 micrograms/L lasted for 4 weeks in the group receiving 20 mg and for at least 6 weeks in those given 30 mg Sandostatin LAR. The pharmacokinetic profile fitted a biphasic drug release model previously described for peptides in similar drug delivery systems. Serum concentrations correlated with the im administered dose. Suppression of GH and insulin-like growth factor I was achieved at serum octreotide concentrations exceeding approximately 600 ng/L. Tolerability was good. Sandostatin LAR holds promise as a valuable drug for the treatment of acromegaly. The results of ongoing long term studies will provide further necessary knowledge of the drug.

A comparison of octreotide, bromocriptine, or a combination of both drugs in acromegaly.

We investigated the pharmacokinetics of bromocriptine and octreotide, both individually and in combination, in 12 patients with active acromegaly. The pharmacodynamics of the drugs were assessed by 12-h profiles of GH secretion and insulin-like growth factor-I (IGF-I) measurements. During the 42-day study period, bromocriptine was administered for 28 days (from day 8; 5 mg, orally, twice daily) and octreotide (200 micrograms, sc, twice daily) from days 15-42. IGF-I levels, 12-h GH, and plasma bromocriptine and octreotide profiles were obtained on days 0, 14, 28, and 42. During bromocriptine treatment, both the area under the GH day curves (AUC) and mean IGF-I decreased to 64% (95% confidence limits, 43-72% and 48-82%, respectively) of initial values. During octreotide treatment, the respective values were 23% (18-30%) and 32% (21-36%), which were greater decreases than those during bromocriptine treatment [36% (95% confidence limits, 32-54%) for AUC for GH and 50% (95% confidence limits, 34-58%) for IGF-I]. With combined treatment, the AUC for GH was reduced to 16% (12-21%) and that of IGF-I to 25% (16-27%) of initial values. This combination was more effective than bromocriptine [25% (95% confidence limits, 22-37%) for AUC for GH and 39% (95% confidence limits, 25-43%) for IGF-I] and octreotide alone [78% (95% confidence limits, 53-89%) for AUC for GH and 78% (95% confidence limits, 57-98%) for IGF-I]. The pharmacokinetic parameters of octreotide were unchanged by the coadministration of bromocriptine. The bioavailability of bromocriptine increased by approximately 40% when bromocriptine was administered together with octreotide compared with administration alone (P < 0.01). Bromocriptine disposition parameters were unaltered. In conclusion, treatment of acromegalics with a combination of octreotide and bromocriptine increases the bioavailability of bromocriptine and reduces both GH and IGF-I levels more effectively than treatment with either drug alone. This presents the possibility of less frequent drug administrations, lower doses of octreotide, and, consequently, lower treatment costs.

A randomized study of SMS 201-995 versus bromocriptine treatment in acromegaly: clinical and biochemical effects.

Twenty-six acromegalic patients were randomized to treatment with either SMS 201-995 or bromocriptine in increasing doses and were investigated before treatment, after 2, 4, and 8 weeks of treatment, and 2 weeks after discontinuation of treatment. There were two dropouts from the bromocriptine group and one from the SMS 201-995 group. Amelioration of clinical signs and symptoms was seen in both groups during treatment. After 8 weeks mean 12-h GH concentrations had declined from 13.8 +/- 5.2 to 2.9 +/- 4.4 (mean +/- SEM) in SMS 201-995-treated and from 18.8 +/- 7.5 to 5.4 +/- 1.2 micrograms/L in bromocriptine-treated patients. Somatomedin-C concentrations fell from 3.04 +/- 0.36 to 1.43 +/- 0.36 in SMS 201-995-treated and from 2.93 +/- 0.40 to 2.13 +/- 0.27 U/mL in bromocriptine-treated patients. Size reduction of the pituitary tumor was seen in one patient receiving bromocriptine. Gastrointestinal glucose absorption was delayed, and insulin secretion suppressed during treatment with SMS 201-995. Hemoglobin-A1 concentrations remained unchanged in SMS 201-995-treated patients, but declined in the bromocriptine group. Side-effects were common, but usually tolerable, with both treatments. It is concluded that both drugs are of benefit in the treatment of acromegaly.

Goodpasture's syndrome. A report of seven patients including long-term follow-up of three who received a kidney transplant.

Seven patients with Goodpasture's syndrome are presented. Bilateral nephrectomy was performed in five patients, and postnephrectomy pulmonary hemorrhage occurred in three. Three nephrectomized patients underwent a successful renal transplant, renal transplantation being postponed until circulating antiglomerular basement membrane antibody had disappeared. The argument is made that pretransplant bilateral nephrectomy in patients with Goodpasture's syndrome is indicated.

Effect of blood transfusions on renal transplantation: study of 191 consecutive first transplants from living related donors.

One hundred ninety-one consecutive living related transplants performed from 1969 to the end of 1978 have been analyzed for the effect of pretransplant blood transfusions. Superior graft survival was observed in transfused patients transplanted with a one HLA haplotype-disparate kidney, whereas no effect of blood transfusions could be observed on the survival of HLA-identical transplants. The frequency of first rejection episodes was significantly reduced in transfused compared to nontransfused one haplotype-mismatched transplants, while no influence of blood transfusions was seen in patients with HLA-identical transplants. The survival of patients was, however, not influenced by previous transfusions. Pretransplant hemodialysis improved graft survival and patient survival; the difference was, however, only significant at 2 years in the one haplotype-mismatched group. When analyzed separately, both blood transfusions and hemodialysis had a beneficial effect on graft survival in one haplotype-mismatched transplants.

Sandostatin LAR: a promising therapeutic tool in the management of acromegalic patients.

A stable and sustained suppression of growth hormone (GH) secretion was noted in 101 patients treated long term with individual doses (20 and 30 mg in 89 patients, 40 mg in 12 patients) of Sandostatin LAR (Sandoz Pharma Ltd, Basel, Switzerland). Doses of 20 mg and 30 mg at 4-week intervals delivered average octreotide concentrations of 1,348 +/- 483 ng/L and 2,631 +/- 1,026 ng/L, respectively, in steady-state conditions and provided adequate control of patients who had been well controlled during treatment with 0.1 mg and 0.2 mg thrice-daily subcutaneous (SC) Sandostatin. Suppression of GH serum concentrations to less than 5 micrograms, 2 micrograms, and even 1 microgram/L was recorded in more patients and more consistently during long-term treatment with Sandostatin LAR than Sandostatin. A marked decrease or even a normalization of insulin-like growth factor-1 (IGF-1) serum concentrations was observed after the first double-blind 10-, 20-, or 30-mg dose of Sandostatin LAR. A progressive improvement was recorded during long-term treatment, with normalization of IGF-1 serum concentrations in 65.3% of patients. A marked clinical improvement was observed in parallel, with 36 of 101 patients (35.6%) becoming asymptomatic after the nineteenth injection of Sandostatin LAR. A greater than 20% shrinkage of the GH-secreting adenoma was also recorded in 12 of 14 patients treated with Sandostatin LAR after receiving only 2 to 4 weeks of treatment with SC Sandostatin and in 11 of 18 patients receiving Sandostatin LAR as adjuvant therapy after failure of surgery. The systemic tolerability of Sandostatin LAR was good, and most adverse events were mild and short term (1 to 2 days). No impairment of thyroid function was detected. Newly occurring gallstones were recorded in four of 101 patients and microlithiasis in four of 101 after up to 30 months of treatment with Sandostatin LAR. Due to its excellent efficacy, good tolerability, convenience of administration, and acceptability by patients, Sandostatin LAR is considered a promising therapeutic tool in the management of acromegalic patients.

Future perspectives of lay organizations.

The article describes the contributions of lay organizations in the field of diabetes. Attention is paid to the often-used terminology like laymen, patients and chronic disease. Further, the major contribution of lay organizations is stressed--their unique knowledge advocacy group for social rights, improvement, and partnership, also concerning the relationship with professionals. Financial restraints for the organization of people with chronic diseases are presented. Conclusions are drawn on the future role of lay organizations.

Influence of HLA-A, B, C, and D matching and pretransplant blood transfusions on kidney graft survival.

A significant influence of matching both for the HLA-A and B and the D/DR antigens on graft survival in patients transplanted with kidneys from living related or cadaveric donors is demonstrated. A generally reduced survival of cadaveric grafts during the last few years may at least in part be explained by the use of more three and four antigen-mismatched donors. The beneficial effect of pretransplant blood transfusions on graft survival in our material is almost nulled when uremic patients, dying while waiting for a transplant, are also considered. In addition, significantly more high-risk patients are included in the nontransfused patient group.

Influence of HLA-A, -B, -C, and -D matching on the outcome of clinical kidney transplantation.

The influence of HLA matching has been studied in the Norwegian material of 142 living related and 311 cadaveric transplants. Graft survival corresponded closely to the degree of HLA haplotype disparity between donors and recipients. Furthermore, graft survival was less in combinations being incompatible for the serologically defined HLA-A and -B antigens as compared to compatible combinations. A weak MLC response, indicating a possible sharing of the HLA-D determinants between donor and recipient, was also associated with superior graft survival, even in the presence of HLA-A and -B disparity. Matching for HLA-C in addition to HLA-A and -B did not seem to improve graft survival.

Renal transplantation in insulin-treated diabetics.

In our view, renal transplantation in the uremic diabetic patient is justified. Recipients should be selected with caution. Patients with both loss of vision and heart disease will only rarely benefit from renal transplantation. Living related donor should be preferred if possible.

Prevalence of diabetes mellitus and impaired glucose tolerance in a rural Palestinian population.

The prevalence of diabetes mellitus and impaired glucose tolerance was investigated in a cross-sectional population-based study in a rural Palestinian population of 500 females and males aged 30-65 years. The prevalence of diabetes was 9.6% and 10.0% in females and males respectively. The prevalence of impaired glucose tolerance was 8.6%; 10.3% in females, 6.2% in males. The prevalence of total glucose intolerance (diabetes mellitus + impaired glucose tolerance) was 18.4%. Our study provides the first baseline data on diabetes mellitus and impaired glucose tolerance in Palestine. The results indicate a high prevalence of glucose intolerance, information that is essential for the implementation of national planning and service provision.

Diabetes mellitus in an urban Palestinian population: prevalence and associated factors.

We investigated the prevalence of diabetes and associated factors in a cross-sectional survey of an urban Palestinian population of 492 men and women aged 30-65 years. The oral glucose tolerance test was used to diagnose diabetes and impaired glucose tolerance. World Health Organization-recommended survey protocols were followed. Diabetes was found in 12.0% of the survey population (including 9.4% previously diagnosed), and impaired glucose tolerance in 5.9%. Logistic regression analysis controlling for age and sex revealed body mass index, waist-to-hip ratio and family history of diabetes to be significantly independently associated with diabetes.

Kidney transplantation in diabetic nephropathy: four years experience.

Since 1972 65 patients with diabetic nephropathy have been evaluated for renal transplantation. Twenty one were not accepted, 6 died before transplantation and 10 are still under observation. Of 28 transplanted patients 13 are alive with functioning graft, and 3 are treated with hospital dialysis. Patient survival at one year was 65% and graft survival 50%.

Influence of blood transfusions on kidney transplant and uremic patient survival.

The influence of blood transfusions on kidney graft survival in 167 first cadaveric transplants and 85 first living related transplants is presented. Blood transfusions had no effect upon kidney graft survival in the patients transplanted with kidneys from living related donors. A significantly better graft survival was observed in the transfused group of patients transplanted with cadaveric kidneys. This beneficial effect was most pronounced in men. When patient survival was analyzed, however, a possible beneficial effect of blood transfusions was almost nulled out when patients dying while waiting for a transplant were included. The majority of these latter patients had been transfused and many had formed HLA antibodies.

Immunosuppressive treatment policies. A) Glucocorticoids: absorption of prednisolone. I. The effect of fasting, food, and food combined with antacids.

Serum concentrations of prednisolone have been measured by radioimmunoassay in 19 healthy volunteers after ingestion of 20 mg prednisolone as four 5 mg tablets. Thirteen subjects were fasting, and 6 had taken a light breakfast. Repeat studies were performed with coadministration of antacid in the 6 non-fasting subjects. The maximum serum concentration of prednisolone was higher, (mean Cmax; fasting: 597 +/- 101 ng/ml, non-fasting: Cmax 489 +/- 56 ng/ml) and the rate of absorption more rapid in the fasting than in the non-fasting subjects (absorption t1/2 fasting: 15.7 +/- 7 minutes, non-fasting: 20 +/- 11.5 minutes). The extent of bioavailability of prednisolone and the rate of elimination were the same in both groups. In the non-fasting groups, the intake of antacid with the tablets had no significant effect on these parameters. This study shows that antacid may safely be coadministered with prednisolone tablets in non-fasting subjects without reducing the rate and extent of bioavailability of prednisolone. It is not known whether the reduction in maximum prednisolone concentration found when the tablets were taken after a meal has any clinical significance.

The effect of 3-4 HLA-A and -B antigen mis-matched cadaveric kidney transplants on graft and patient survival.

During the period 1969 to 1978 survival of recipients of 1st cadaveric renal grafts improved. This improvement occurred in spite of a sharp increase in high risk patients accepted for transplantation, including patients with high age, diabetic nephropathy and advanced arteriosclerotic disease. In the same period 1st graft survival decreased. The declining graft prognosis was related to the acceptance of 3-4 HLA-A and B incompatible grafts from 1973 onwards. Grafts with 0-2 incompatibilities had a stable survival during the whole 10-years period. The group of patients receiving grafts with 3-4 incompatibilities, however, included significantly more patients with diabetic nephropathy and age above 55 years. Further analysis demonstrated that the inferior graft prognosis was caused by a combined effect of HLA-mismatched grafts and the number of high risk patients. The distribution of antibodies at retransplantation (2nd graft) was similar whether the lost 1st graft was compatible for 0-2 or 3-4 HLA antigens. Also the prognosis of retransplantation was similar in the two groups.