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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty patients with primary GH resistance (Laron syndrome) due to molecular defects of the GH receptor or post-receptor pathways were followed from infancy through adulthood. This condition leading to long-term insulin-like growth factor-I (IGF-I) deprivation caused marked growth retardation (-4 to 8 height SD), acromicia, organomicria, retarded development of the skeletal and muscular systems, a small cranium, slow motor development, and impairment of intellectual development in some of the patients. In addition, there was progressive obesity, insulin resistance, a tendency for hypoglycemia, followed later in life by hypercholesterolemia and by glucose intolerance and even diabetes. IGF-I treatment of children with Laron syndrome, by our and other groups (150-240 microg/day sc), stimulated growth (8 cm in the first year and 4-5 cm in the following years) and normalized the biochemical abnormalities. Overdosage led to adverse effects such as hypoglycemia, edema, swelling of soft tissues, and hyperandrogenism. It is concluded that primary IGF-I deprivation induces severe auxological, biochemical, and hormonal changes, the only treatment being biosynthetic IGF-I administration.
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PMID:The essential role of IGF-I: lessons from the long-term study and treatment of children and adults with Laron syndrome. 1059 94

Recent diagnostic and pharmacologic developments have focused renewed attention on polycystic ovary syndrome. Clinical features of the syndrome include anovulation, hyperandrogenism and menstrual dysfunction, but several other abnormalities, including hyperinsulinemia, luteinizing hormone hypersecretion, elevated testosterone levels and acyclic estrogen production, have been documented. Accompanying obesity and lipid abnormalities compound the risk of developing diabetes mellitus or cardiovascular disease, and chronic anovulation increases the risk for endometrial cancer. A careful history and physical examination should guide diagnostic testing. Slowly progressive hyperandrogenic symptoms with anovulation of peripubertal onset often represent polycystic ovary syndrome. Treatment goals include symptom management and the identification and prevention of potential cardiovascular risks. Treatment should take into account the patient's desire for fertility. Advances in transvaginal ultrasonography and infertility treatments, including newer medications, have facilitated assisted reproduction in patients with polycystic ovary syndrome. Ongoing pharmacologic research focusing on the treatment of insulin resistance appears promising in reversing the longterm complications of the syndrome.
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PMID:Polycystic ovary syndrome: it's not just infertility. 1099 32

The current recommendation for strict metabolic control of type 1 diabetes mellitus requires the administration of supraphysiological doses of insulin, which might result in insulin-mediated stimulation of androgen synthesis, as occurs in insulin-resistant states. At present, the prevalence of hyperandrogenic disorders in women with type 1 diabetes mellitus is unknown. Eighty-five women with type 1 diabetes mellitus were evaluated for symptoms and signs of hyperandrogenism. In 68 of the patients, several serum androgen and hormone concentrations were measured. The polycystic ovary syndrome (PCOS) was defined by the presence of menstrual dysfunction, together with clinical and/or biochemical evidence of hyperandrogenism, and exclusion of other etiologies. Eighteen healthy women, menstruating regularly, served as controls for the androgenic profiles. Thirty-three patients (38.8%) presented hyperandrogenic disorders (16 had PCOS, and 17 had hirsutism without menstrual dysfunction). Type 1 diabetic patients with PCOS presented increased serum total and free testosterone concentrations, and serum androstenedione levels, but had normal serum sex hormone-binding globulin and dehydroepiandrosterone-sulfate levels. Hirsute type 1 diabetic women without menstrual dysfunction presented normal serum androgen levels. There were no significant differences between hyperandrogenic and nonhyperandrogenic type 1 diabetes mellitus women in clinical variables such as the duration of diabetes, age at diagnosis of diabetes, conventional or intensive insulin therapy, mean daily insulin dosage, or metabolic control. In conclusion, women with type 1 diabetes mellitus have a high prevalence of hyperandrogenic disorders, including PCOS and hirsutism.
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PMID:High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus. 1109 51

Human sex hormone-binding globulin (SHBG) regulates the cellular bioavailability of SHBG-bound steroid hormones. Subtle decreases in plasma SHBG levels during puberty have a perceptible effect on the androgen-estrogen balance. This SHBG decrease is more pronounced in girls with premature pubarche who are at risk to develop functional ovarian hyperandrogenism as well as insulin resistance syndrome. Insulin is a potent inhibitor of SHBG production in the liver, and there is now evidence that SHBG is a marker of hyperinsulinemia and insulin resistance that can be associated in both obese and non-obese patients with polycystic ovary syndrome. Therefore, low SHBG could be a useful tool for identifying presymptomatic individuals with diabetes mellitus type 2 including those with androgen disorders.
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PMID:Sex hormone-binding globulin during puberty in normal and hyperandrogenic girls. 1111 69

In reviewing the epidemiology of recurrent abortion (RAB), we believe it is necessary to consider the epidemiology of spontaneous abortion (SAB) as well, since it is clear that even a single pregnancy loss increases the risk for a subsequent abortion. In addition, any attempt to identify epidemiologic risk factors for SAB or RAB must deal with the fact that at least 50% of SABs are associated with genetic abnormalities. Given that most epidemiologic studies have not distinguished karyotypically abnormal abortuses, risk factors are likely to be underestimated. Nevertheless, there is fair agreement that a variety of factors may increase risk for SAB or RAB, including advanced maternal age, single gene mutations such as PKU or G6PD deficiency, structural abnormalities of the uterus, poorly controlled diabetes, antiphospholipid syndrome, and smoking. More controversial is the role of luteal phase defect or hyperandrogenism, alloimmune factors, genital infections, caffeine or alcohol use, and trace element or chemical exposure from tap water or in the workplace. Besides better designed epidemiologic studies to detect modifiable risk factors for SAB or RAB, there is a clear need for clinical trials of therapy for RAB which meet minimum epidemiologic standards including randomization, double-blinded (when possible), and placebo-controlled (when ethical).
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PMID:The epidemiology of recurrent pregnancy loss. 1135 91

Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.
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PMID:Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. 1147 39

Epidemiological: higher coronary risk in female diabetic patients than in male diabetic patients. Physiopathological: disturbance of lipid metabolism and endothelial nitric oxide (NO) production, seen in both menopausal and diabetic subjects. Hormonal: hyperandrogenism and excessively high blood oestradiol levels in diabetic menopausal women in relation to non-diabetic menopausal women. HRT in menopausal diabetic women Efficacy against climacteric disorders and osteoporosis. No major risks since the effects on lipoproteins are not significant and there are some positive effects on hepatic glucose production during hyperinsulinaemic clamp, provided triglycerides are below 2 mmol/l. Relatively positive effects have been noted in cohort studies such as the Nurses' Health Study and in a study measuring carotid intima-media thickness, but marked bias occurred in recruitment. HRT and coronary disease in diabetic and non-diabetic women Harmful effects were noted, particularly in the HERS study, with a higher incidence of fatal and non-fatal thromboembolic and/or coronary events. Other studies are underway using both conjugated equine estrogens (Women's Health Initiative) and SERMs (raloxifen and tamoxifen).
Diabetes Metab 2001 Sep
PMID:[Hormone replacement therapy at menopause in the diabetic woman]. 1178 43

Recent findings suggest substantial metabolic sequelae to polycystic ovary syndrome (PCOS), including risk of diabetes and cardiovascular disease. Primary treatment of the metabolic sequelae should be the focus of the clinician. The definition of PCOS has been expanded from a disorder that presents at menarche and ends at menopause to a disorder that may be present from birth to senescence. The earliest recognized PCOS phenotype to date is premature pubarche characterized by excessively elevated levels of dehydroepiandosterone sulfate and hyperinsulinemia. Such girls are at high risk to develop the full PCOS phenotype, including ovarian hyperandrogenism and chronic anovulation. A fasting glucose-to-insulin ratio of < 7 is a useful index of insulin resistance in adolescents. However, each patient should be evaluated for glucose intolerance and lipid abnormalities on a regular basis by completing a 2-hour oral glucose tolerance test and a fasting lipid profile. Primary prevention of diabetes and cardiovascular disease by lifestyle modifications, regular exercise, and a balanced diet are of utmost importance, especially in adolescents who have the opportunity to establish healthy habits before entering adulthood. The role of insulin-sensitizing medications is still under study. Although no clinical trials over 6 months in duration have assessed the long-term efficacy of metformin use in adolescents, short-term trials have shown promising effects in lowering insulin secretion, improving insulin sensitivity, restoring normal menstrual cycles, and correcting lipid abnormalities.
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PMID:Polycystic ovary syndrome in adolescents. 1184 56

Non-insulin-dependent diabetes mellitus (NIDDM), type 2 diabetes mellitus, was once considered rare in children and adolescents. This is no longer true as NIDDM now accounts for 5% to 45% of new cases of diabetes mellitus in the pediatric age group. Most commonly, this disease is seen in obese children with a family history of NIDDM, and particularly in African American, Native American, and Hispanic children. Acanthosis nigricans and hyperandrogenism are sometimes seen. Pediatric health care providers should be aware of the factors that contribute to the development of NIDDM in children as well as the approaches to diagnosis and treatment.
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PMID:Screening, diagnosis, and management of non-insulin-dependent diabetes mellitus in adolescents. 1186 92

Even small increases in the frequency of thrombotic disease in users of OCs have general health impact because of their widespread use, which is currently expanding to potential risk groups. The present investigations were launched to study the effects of OCs containing 20-40 micrograms of EE combined with the latest developed gonane progestogens on biochemical risk markers within metabolic systems involved in the development of arterial thrombotic disease. The studies included evaluation of carbohydrate and lipid metabolism as well as the haemostatic system and were performed in non-diabetic women and in women with IDDM, who are prone to the development of arterial thrombosis. In the evaluation of the carbohydrate metabolism in non-diabetic women, we found no effect on fasting glucose or insulin and no effect on the insulin response to oral glucose in women using monophasic OCs containing EE combined with DSG or GST. This contrasts the evaluation of triphasic OCs containing EE combined with GST or NGT, which increased fasting insulin and reduced insulin sensitivity without affecting the glucose-effectiveness or the beta-cell function. Impaired glucose tolerance developed in 10% of the women after 6 months. These finding suggest that OCs are able to induce a state of insulin resistance, which should be considered in the prescription for women with potential disturbed insulin sensitivity or reduced beta-cell secretory capacity e.g. women with ovarian hyperandrogenism, obesity, previous GDM or perimenopausal women. We found no change in glycaemic control in 22 women with well-regulated IDDM treated with a monophasic combination of EE and GST for one year and none of the women developed microalbuminuria during treatment. In the women with diabetes we observed an increase in fasting levels of triglycerides, a decrease in LDL-cholesterol, and unchanged concentrations of total cholesterol and HDL-cholesterol during treatment. In non-diabetic women treated with the same compound or an OC containing EE and DSG we found similar changes in triglycerides and total cholesterol, but increased levels of HDL-cholesterol and unchanged LDL-cholesterol concentrations. In the women with IDDM there was a negative correlation between daily insulin requirement and HDL-cholesterol before and during treatment, but no other statistically significant correlation between estimates of glycaemic control and lipids and lipoproteins were observed. In the non-diabetic women, changes in the haemostatic system included an increase in the procoagulant factors fibrinogen and Factor VIIc; the concentration of active t-PA increased, mainly because of decreased inhibition by PAI-1. The ratio between molecular markers of the activity of the coagulation system and the efficacy of fibrinolysis was unchanged. This was also found in the women with IDDM, who showed evidence of increased fibrin formation and an attenuated fibrinolytic response during treatment. The regulation of the t-PA/PAI system was studied in non-diabetic women in order to elucidate if the effects of OCs are caused by a direct effect on synthesis or clearance of these variables or if they are secondary to changed insulin sensitivity, as described in individuals with atherosclerosis. We found no indications that insulin resistance is involved in the regulation of t-PA and PAI-1 antigen levels, neither before nor during intake of OCs. We showed, however, that the decreased t-PA antigen concentration observed in OC users is caused by reduced synthesis outside the splanchnic circulation. The studies indicate that low-dose OCs containing newer gonane progestogens are able to induce insulin resistance and to impair glucose tolerance. Lipoproteins were not adversely influenced by the OCs neither in the diabetic nor the non-diabetic women; on the contrary, there was a tendency towards increased plasma levels of HDL-cholesterol and decreased LDL-cholesterol which are associated with a decreased risk of atherosclerosis. The changes observed within the haemostatic system were in accordance with a maintained balance between coagulation and fibrinolysis although the rate of fibrin formation may be increased in the women with IDDM. Irrespective of OC use, the interrelationships between metabolic systems in young non-diabetic women are different from those reported in individuals with atherosclerosis or insulin resistance. The effects of OCs on the t-PA/PAI system seem to be mediated by a direct effect on the vessel wall and not by changes in the hepatic clearance. The present findings were obtained in diabetic women without vascular complications, so the conclusion that women with IDDM can use OCs without metabolic alterations of known clinical significance is therefore restricted to those without evidence of diseased vessels. When evaluating the results obtained in the non-diabetic women, it should be remembered that women with recognised risk factors were excluded. The results may therefore be of limited value when evaluating the risk of arterial thrombosis in predisposed populations. In healthy individuals, the present integrated evaluation of biochemical markers does not indicate an increased risk of arterial thrombosis during use of low-dose OCs containing newer gonane progestogens; thus, the findings are in accordance with the recent epidemiological studies on these compounds. The application of relevant biochemical markers facilitate the understanding of the non-reproductive effects of sex steroids which have increasing importance because of their expanding use, not only as contraceptives, but also in the treatment of benign gynaecological disorders, as hormone replacement therapy and as prophylactic agents against specific degenerative conditions. Moreover, they may prove to be helpful in the future identification of women, who have increased susceptibility to the metabolic effects of sex steroids due to genetic predisposition.
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PMID:Pharmacodynamic effects of oral contraceptive steroids on biochemical markers for arterial thrombosis. Studies in non-diabetic women and in women with insulin-dependent diabetes mellitus. 1189 23


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