Gestational diabetes mellitus and hypertension in pregnancy: hemodynamics and diurnal arterial pressure profile

We characterised the 24-h arterial pressure (AP) profile and the left ventricular (LV) structures and functions in pregnant women with pregnancy-induced hypertension (PIH) or gestational diabetes mellitus (GDM). Thirty pregnant women after 20 weeks' gestation--(10 normotensive; 10 with PIH; and 10 with GDM)--were investigated haemodynamically using 24-h AP monitoring and Doppler echocardiography for determination of LV structures and functions, both systolic and diastolic. The PIH women had significantly higher AP determinations throughout the 24 h, with no change in the diurnal variation, ie, nocturnal decline and early morning peaks. The LV mass was greater in PIH and GDM than in the normotensive women, despite normal AP in GDM. The increased LV mass in GDM was mainly due to LV dilatation and not to increased thickness of its walls. In PIH, the increase in AP was due to peripheral vasoconstriction, while cardiac output was preserved. The LV systolic functions did not differ among the three groups. However, a slight reduction in the myocardial contractility was found in PIH and GDM. The LV relaxation was significantly impaired in both PIH and GDM. Thus, GDM and PIH, although differing in their 24-h AP profile, are characterised by LV hypertrophy and reduction in diastolic function.     

Gestational diabetes mellitus and subsequent development of overt diabetes mellitus

GDM develops in 1-3% of all pregnancies. Women with GDM are characterized by a relatively diminished insulin secretion coupled with a pregnancy-induced insulin resistance primary located in skeletal muscle tissue. The cellular background for this insulin resistance is not known. The binding of insulin to its receptor and the subsequent activation of the insulin receptor tyrosine kinase have significant importance for the cellular effect of insulin. Thus, the pathogenesis to the insulin resistance was studied by investigating insulin receptor binding and tyrosine kinase activity in skeletal muscle biopsies from women with GDM and pregnant controls. No major abnormalities were found in GDM wherefore it is likely that the insulin resistance is caused by intracellular defects distal to the activation of the tyrosine kinase. Glucose tolerance returns to normal postpartum in the majority of women with GDM. However, previous studies, in populations quite different from a Danish population, have shown that women with previous GDM have a high risk of developing overt diabetes mellitus later in life. Hence, we aimed to investigate the prognosis of women with previous GDM with respect to subsequent development of diabetes and also to identify predictive factors for the development of overt diabets in these women. A follow-up study of diet treated GDM women diagnosed during 1978 to 1985 at the Rigshospital, Copenhagen was performed. Glucose tolerance was evaluated in 241 women (81% of the GDM population) 2-11 years after pregnancy. Abnormal glucose tolerance was found in 34.4% of the women (3.7% IDDM, 13.7% NIDDM, 17% IGT) in contrast to a control group where none had diabetes and 5.3% had IGT. Logistic regression analysis identified the following independent risk factors for later development of diabetes: a high fasting glucose level at diagnosis of GDM, a delivery more than 3 weeks before term, and an abnormal OGTT 2 months postpartum. Low insulin secretion at diagnosis of GDM was also an independent risk factor. The presence of ICA and GAD-autoantibodies in pregnancy was associated with later development of IDDM. In another study the following techniques: hyperinsulinaemic euglycaemic clamp, indirect calorimetry and tritiated glucose infusion were used to evaluate insulin sensitivity in glucose tolerant nonobese women with previous GDM and controls. A decreased insulin sensitivity due to a decreased non-oxidative glucose metabolism in skeletal muscle was found in women with previous GDM. Hence, the activity of three key enzymes in intracellular glucose metabolism (GS, HK and PFK) was studied in skeletal muscle biopsies obtained in the basal state and after 3 h hyperinsulinaemia, with the aim to identify the cellular defects causing the decreased insulin sensitivity. However, no abnormalities in enzyme activity was found. The same group of previous GDM women had a relatively reduced insulin secretion evaluated by the IVGTT. A longitudinal study of 91 GDM women showed a relatively reduced insulin secretion to oral glucose in pregnancy, postpartum as well as 5-11 years later. Thus the present review has shown that even nonobese glucose tolerant women with previous GDM are characterized by the metabolic profile of NIDDM i.e. insulin resistance and impaired insulin secretion. Hence, the combination of this finding together with the significantly increased risk for development of diabetes indicates that all women with previous GDM should have a regular assessment of their glucose tolerance in the years after pregnancy. The first OGTT should be performed around 2 months postpartum in order to diagnose women already diabetic and to identify women with the highest risk for later development of overt diabetes. Women with previous GDM comprise a target group for future intervention trials with the aim to prevent or delay development of NIDDM and IDDM.     

Outcome of post-term pregnancy: a matched-pair case-control study

Insulin resistance is a feature of non-diabetic relatives of non-insulin-dependent diabetic (NIDDM) families. Tumour necrosis factor-alpha (TNF alpha) expression is linked with insulin resistance, and is under strong genetic control. We examined the relationship between insulin resistance and two polymorphisms of the TNF alpha promoter region (positions -238 and -308). Non-diabetic relatives (n = 123) of NIDDM families and control subjects (n = 126) with no family history of diabetes were studied. Insulin resistance was determined by homeostasis model assessment (HOMA) and short insulin tolerance test (ITT), and genotyping was by restriction digest. The -238 polymorphism (TNFA-A allele) was carried by 14 relatives and 11 control subjects, and all were heterozygotes. To examine the relationship between the -238 polymorphism and insulin resistance independent of potentially confounding factors, the relatives with the TNFA-A allele were individually pair-matched for age, sex, waist-hip ratio, body mass index, and glucose tolerance with relatives homozygous for the wild-type allele. Relatives with the TNFA-A allele had decreased insulin resistance (HOMA index: 2.0, 3.6 +/- 2.1 [means +/- SD of differences], p = 0.03), and this was true for comparable pair-matched control subjects (HOMA index: 1.1, 1.9 +/- 0.8, p = 0.01). Combining relative (n = 7) and control (n = 4) pairs that had undergone an ITT, subjects with the TNFA-A allele had an increased K(ITT) (3.8, 3.0 +/- 1.0%/min, p = 0.04) similarly indicating decreased insulin resistance. There was no significant relationship between the -308 polymorphism and insulin resistance. We conclude that the TNFA-A allele is associated with decreased insulin resistance as assessed by two independent methods, and may protect against the future development of NIDDM in susceptible individuals.     

Gallstones and diabetes: a case-control study in a free-living population sample

Data on the association between cholelithiasis and diabetes often are controversial and are mostly based on autopsies or on hospital series. Therefore, we designed a case-control study to determine the prevalence of diabetes mellitus in a group of subjects with gallstones or having undergone cholecystectomy (cases) and compared these with a control group of subjects without gallstones, selected during an epidemiological study performed on a free-living population sample. The subjects were matched for sex, age, and body mass index. We enlisted 336 cases and 336 controls, aged 30 to 69 years. All subjects with fasting glycemic levels of < 140 mg/dL and without a documented history of diabetes were submitted to a simplified oral glucose tolerance test (OGTT). All subjects who underwent OGTT were classified according to the National Diabetes Data Group (NDDG) criteria. The prevalence of diabetes in the subjects affected by gallstone disease was significantly higher than that in controls (11.6% vs. 4.8%; odds ratio [OR], 2.55; 95% confidence interval [CI], 1.39-4.67). Diabetes was more frequent in subjects with gallstone disease than in the control group, even according to sex (18.3% vs. 9.9% for men: OR, 2.03; 95% CI, 0.99-4.2; 9.3% vs. 2.6% for women: OR, 3.85; 95% CI, 1.4-10.6). We conclude that an altered glucose metabolism may increase the risk of developing cholelithiasis in certain subjects.     

Gestational diabetes: a challenge for the future

It is well established that pregnancy is associated with temporary changes in maternal metabolism which include a decrease in maternal insulin sensitivity to values similar to those associated with Type 2 diabetes. Fasting glucose concentrations fall throughout pregnancy, postprandial values rise. The maintenance of glucose tolerance in pregnancy requires a two- to three-fold increase in postprandial maternal insulin secretion. Glucose intolerance develops in women unable to compensate for the metabolic changes incurred by pregnancy. Increasing maternal hyperglycaemia is associated with increasing pregnancy morbidity and an increased likelihood of subsequent diabetes in the mother. In addition, maternal hyperglycaemia has a direct effect on the development of the fetal pancreas and is associated with an increased susceptibility to future diabetes in the infant, an effect which is independent of genetic factors. Gestational diabetes mellitus (GDM) is defined as glucose intolerance first recognized in pregnancy, and by definition includes a small number of women with previously unrecognized diabetes or impaired glucose tolerance (IGT). Figures on the prevalence of GDM vary between maternity units, depending on screening methods and the ethnic distribution of the populations. However, in a comprehensive study of a multi-ethnic antenatal population in inner London, UK it was found that only 2% of pregnant women develop significant glucose intolerance. Obstetricians and physicians debate the importance of identifying this 2% of women. The lack of agreed criteria for diagnosing gestational diabetes and the questionable obstetric benefits of treating all women with mild disturbances of glucose tolerance in pregnancy has resulted in few UK centres undertaking universal screening for GDM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epidemiology of diabetes mellitus in the elderly in northern Greece: a population study

This population based study was undertaken to ascertain the overall prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in the elderly using the WHO criteria. The role of obesity in the development of DM or IGT has been investigated for both sexes per decade of age. Furthermore the potential for DM to increase with age, as has been suggested before, has been evaluated using the IGT as a proportion of total glucose intolerance (IGT/TGI) for the same parts of the tested sample. From the 647 persons registered as elderly people in a small town in northern Greece (total population 5875 people), 66 persons did not participate in this survey. Fifty-six subjects (9.7%) had previously diagnosed DM. The remainder were tested using fasting blood glucose measurements or an oral glucose tolerance test (OGTT). The prevalence of previously undiagnosed DM according to fasting blood glucose values or after 2 h of 75 g load values was 10.1% and 9.3%, respectively. Thus the overall prevalence of DM was 29.1% and of IGT was 15.1%. These data support an increased frequency of DM (65% previously undiagnosed) and IGT in the elderly, whereas this population's susceptibility seems to decline in the older groups for both sexes. Obesity remains a risk factor for DM and IGT particularly among the younger groups although its role has been found to decline with age.     

Postsurgical mediastinitis: a case-control study

We report the results of a case-control study of postsurgical mediastinitis (PSM) that we conducted from 1985 to 1993. The incidence of PSM was 2.2% (81 of 3,711 cases who underwent sternotomy); we analyzed the findings for 73 cases and 73 controls. Univariate analysis revealed that the risk factors for PSM were emergency surgery (27% of cases vs. 13% of controls), New York Heart Association functional class IV (46.5% vs. 21.9%), heart transplantation (12% vs. 0), and coronary artery bypass graft (CABG) surgery (60% vs. 41%). The incidences of fever, reoperation for bleeding, pacemaker placement, use of vasoactive drugs, prolonged mechanical ventilation, use of central lines, and treatment in the intensive care unit were also higher for cases. Multivariate analysis identified the following independent risk factors for PSM: reoperation (risk ratio [RR], 9.2), need for vasoactive drugs (RR, 3.5), CABG surgery (RR, 3.2), and fever that persisted after the third postsurgical day (RR, 406). The related mortality was 13.7%, and death was significantly more frequent among cases (17.7%) than among controls (2.7%). Multivariate analysis identified the following independent risk factors for mortality: bacteremia (RR, 21.5), the use of an intraaortic balloon (RR, 14.9), advanced age (RR, 1.14 per year), and prolonged mechanical ventilation (RR, 1.1 per day).     

Childhood polymyositis: a case-control study

A case-control epidemiologic study of childhood polymyositis is presented. Parents of 42 cases of childhood polymyositis were interviewed along with parents of controls matched for sex and age. Extensive review of past medical history, animal exposure history, residential and family history, and immunization history failed to reveal any significant differences between the two groups. The only suggestive difference was exposure to bacteriologically confirmed streptococcal diseases in 20 cases as compared to 13 controls.     

Intradermal tophi in gout: a case-control study

OBJECTIVE: To describe the characteristics of intradermal tophi in patients with gout and search for factors associated with their development. METHODS: This is a case-control study of patients with gout: cases (Group A, n = 21) had intradermal (not subcutaneous) plaques of monosodium urate (MSU) crystals located in sites distant to articular or paraarticular structures, and controls (Group B, n = 42) had gout but no intradermal tophi. Both Group A and Group B were paired by sex, age (+/-5 years), and duration of the disease (+/-3 years). Analysis included serum and urinary uric acid levels at first visit, radiographic stage of gout, the presence of associated diseases, and previous therapy, specifically, chronic glucocorticoid and diuretic usage. RESULTS: Intradermal tophi were located in the legs, forearms, buttocks, thighs, arms, and abdominal wall. Patients in Group A had a greater number of nonintradermal tophi in common sites (11.9+/-12.5 vs. 4.2+/-7.9, mean +/- SD; p = 0.018), decreased glomerular filtration rate (46.74+/-25.11 vs. 70.87+/-30.18 ml/min; p = 0.042), advanced radiographic changes (57.2 vs. 7.1%; p = 0.0001), and longterm glucocorticoid self-medication (76 vs. 36%; p = 0.006). We found no differences in other associated diseases between groups. CONCLUSION: Intradermal tophi were commonly found in the legs and forearms, and less frequently in the buttocks, thighs, and abdominal wall of gouty patients, and were associated with longterm self-prescribed glucocorticoids and chronic renal failure. The occurrence of intradermal tophi in these patients appeared to correlate with advanced disease.     

Evidence for different clinical subtypes of type 1 diabetes mellitus: a prospective study

Goal of this study was to compare the quantitative coronary arteriographic (QCA) results obtained with the Philips DCI/ACA analytical software package with those from postmortem casts in an animal experimental setting. Standard digital coronary arteriograms were obtained from 6 mongrel dogs. After the imaging procedure, the dogs were sacrificed and casts were made of the coronary trees by filling the vessels with a mixture of radio-opaque barium and silicone gel at a fixed pressure of 100 mmHg. Vessel diameters were measured from the digital arteriograms at a total of 118 selected locations with the ACA package. Thin slices were cut from the casts at these same measurement locations and the areas of the cross sections were obtained by manual tracing of the outline of each slice in an approximately 40 x magnified image. From these cross-sectional areas, cast diameters were derived using the formula for circular cross-sections. Cast diameters ranged in size from 0.69 to 3.30 mm. The systematic error between the measurements was found to be 0.058 mm; (p < 0.015) and the standard deviation of the signed difference 0.255 mm; the correlation coefficient was r = 0.91. The largest error sources are supposed to be the slight differences in the selection of identical positions in the X-ray images and on the casts, and the 'out-of-plane' magnification for a number of vessel locations. This postmortem study demonstrates that the diameters of coronary vessels can be measured from digital arteriograms with the DCI/ACA package with a high degree of accuracy and precision.     

A necropsy study of diabetes mellitus in natal blacks

During a period of 10 years (1965 - 1974) necropsies on 126 Black diabetic patients were performed at King Edward VIII Hospital, Durban. Metabolic factors accounted for 39% of deaths and infection for 34% of all deaths in diabetes mellitus. Sixty-two per cent of the patients who died were below the age of 55 years. These findings are similar to those pertaining in the pre-insulin era.     

Diminished insulin clearance during late pregnancy in patients with type I diabetes mellitus

OBJECTIVE: Published data on bone metabolism in diabetes mellitus are conflicting. We have measured pyridinium crosslinks, biochemical markers of bone resorption, in order to evaluate bone resorption in diabetes mellitus. We also wished to investigate whether, as a consequence of chronic hyperglycaemia, pyridinoline is glycosylated to a greater extent in patients with diabetes mellitus. DESIGN AND PATIENTS: This cross sectional study included 142 patients (64 males, 78 females) with insulin dependent and non-insulin dependent diabetes mellitus (IDDM and NIDDM). These patients were compared to a healthy control group of 99 individuals (39 males and 60 females). MEASUREMENTS: Pyridinium crosslinks, glycosylated, free and total pyridinoline (gPYD, fPYD, tPYD) and free and total deoxypridinoline (fDPD, tDPD) were measured in a spot urine sample by high performance liquid chromatography (HPLC). Urinary creatinine, albumin and glucose were also measured. RESULTS: In the diabetic group, values of urinary gPYD and tDYD were significantly lower than in controls. gPYD excretion was lowest in patients with severe glycosuria. Free pyridinium crosslinks, both fPYD and fDPD, were excreted to a significantly lower extent. The molar ratio of tPYD to tDPD was significantly increased in diabetes mellitus. CONCLUSIONS: Decreased excretion of tDPD suggests low bone resorption in IDDM and NIDDM. Pyridinoline is not glycosylated to a greater extent in diabetes mellitus and tends to be decreased in proportion to the degree of glycosuria. Excretion of gPYD, fPYD and fDPD is depressed in severe glycosuria. Diminshed degradation to the final products, fPYD and fDPD, might represent increased resistance to enzymatic activity or diminished enzymatic activity. The increased molar ratio tPYD/tDPD in urine suggests an increased ratio in bone collagen in diabetes mellitus.     

Diabetes mellitus in pregnancy

Physiologic changes that occur during pregnancy are diabetogenic. If diabetes does not exist before pregnancy, it may become evident, and if diabetes pre-exists, it becomes aggravated. The changing insulin requirements and propensity for ketoacidosis require weekly visits and careful urine testing on a daily basis by the mother. In addition, microvascular complications of diabetes must be carefully monitored. Delivery is planned progressively early in the pregnancy according to diabetic class. Hospitalization is necessary one week before anticipated delivery. Urinary estriol tests, OCT, amniocentesis, and ultrasound are all helpful in managing the pregnancy. Delivery of the fetus and placenta results in a profound fall in the insulin requirement. The neonate should be carefully observed during the first few days of life because of the increased frequency of complications.     

Racial disparity in pregnancy outcomes: analysis of black and white teenage pregnancies

The pregnancies of black women are complicated by adverse outcomes such as prematurity and low birth weight at twice the rate of complications in pregnancies of white women. Although the cause of this racial disparity is unknown, it is most likely multifactorial. The disparity in outcomes has been found in many studies despite implementation of controls for the factors of age, socioeconomic status, and access to health care. We hypothesized that the increased incidence of adverse outcomes may be strongly affected by adequacy of prenatal care. We investigated the effects of comprehensive prenatal care delivered at the University of North Carolina-Chapel Hill Teenage Obstetric Clinic. The gestational age at the onset of prenatal care and the mean number of prenatal visits were the same for black and white teenagers. Among 183 teenagers we found no significant difference between black and white pregnancies for the outcomes of premature labor, premature delivery, fetal death, neonatal mortality, or hypertensive diseases. The mean gestational age at delivery was 38.3 weeks and 39.1 weeks for black and white women, respectively. The mean birth weight was 3126 gm and 3272 gm for black and white women, respectively. There was a trend (p < 0.09) toward more low birth weight infants in white women: 7% for black infants and 12% for white infants. We believe that comprehensive prenatal care significantly lessens the racial disparity in pregnancy outcomes between black and white adolescent women.     

Glucosuria of pregnancy: frequency of diabetes mellitus and renal glucosuria (author's transl)

From 1974 to 1979 352 pregnant women were referred to our diabetic outpatient clinic because of glycosuria during pregnancy. In 118 women (34%) oral glucose tolerance tests revealed a pathologic glucose tolerance. In 234 pregnant women (66%) a "renal glycosuria of pregnancy" was found to be the cause for the observed glycosuria. A pathologic glucose tolerance was relatively more frequent in the 3rd trimenon, whereas renal glycosuria was observed to be more frequent in the second trimenon.     

Fibrinogen, fibrinolysis and diabetes mellitus: a comment

A synthetic diet, developed for tsetse flies and fed to Tabanus nigrovittatus Macquart before the 2nd gonotrophic cycle, supported complete egg maturation. T. nigrovittatus is autogenous only during the 1st cycle. Overall, 52% of females fed bovine blood and 46% fed the synthetic diet produced mature, stage 10 follicles. Of these, 76% of the blood-fed females and 65% of those fed the synthetic diet laid egg masses, all of which hatched. The median adult survivorship was 9 d for blood-fed and 8 d for those fed the synthetic diet.