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

Severe insulin resistance type A is due to mutations in the insulin receptor gene and is characterized by glucose intolerance or diabetes mellitus, despite extreme hyperinsulinemia, virilization and acanthosis nigricans. At present, there is no therapy for this condition. Recently, we showed that glucose levels in three such patients are promptly lowered by an i.v. bolus of recombinant human insulin-like growth factor I (rhIGF-I). In the present study, we investigated two of these rare patients again and determined fasting and postprandial glucose, insulin, C-peptide, proinsulin and lipid levels during five control, five treatment and three wash-out days while on a constant diet. Treatment consisted of 2 x 150 micrograms rhIGF-I/kg sc per day, which elevated total IGF-I levels 4.5-fold above the control. Fasting glucose levels (days 1-5) in the two patients were 9.6 +/- 1.3 and 9.2 +/- 1.2 mmol/l, respectively, and fell to 4.4 +/- 0.4 and 5.1 +/- 0.5 mmol/l on treatment days 8-10. Fasting insulin (2950 +/- 450 and 690 +/- 125 pmol/l), C-peptide (2217 +/- 183 and 1317 +/- 235 pmol/l) and proinsulin control levels (125 +/- 35 and 66 +/- 0 pmol/l) also decreased by approximately 65% during rhIGH-I treatment, as did the respective postprandial levels. Lipid levels hardly changed at all. In conclusion, IGF-I appears to correct partially some metabolic sequelae of severe insulin resistance and may, hence, be used as a new therapeutic agent.
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PMID:Beneficial metabolic effects of insulin-like growth factor I in patients with severe insulin-resistant diabetes type A. 792 Dec 9

Obesity, a phenotype having high heritability in humans, constitutes the major risk factor predisposing an individual to non-insulin-dependent diabetes mellitus (NIDDM). However, most obese humans do not develop NIDDM, indicating that diabetogenesis entails a complex interaction between obesity genes and other predisposing susceptibility traits. The possible nature of some of these background modifiers is being elucidated by analysis of genetically obese mice. Mutations at loci on six different mouse chromosomes produce obesity, but development of insulin-resistant diabetes requires an interaction between the obesity mutation and other factors in the genetic background. Analysis of the interaction between three distinct obesity genes expressed on the same genetic background has shown that virilization of hepatic sex steroid metabolism mediated via aberrant shifts in sex steroid sulfotransferase activities is a prerequisite for diabetogenesis. The analogies between the development of a hyperandrogenized tissue state in obese mice with obesity-diabetes syndromes in humans are discussed.
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PMID:Obesity genes and diabetes induction in the mouse. 835 93

Extreme insulin resistance occurs in patients with primary defects in insulin action at the receptor or postreceptor levels. The condition commonly is associated with acanthosis nigricans and ovarian masculinization. Despite a marked increase in insulin secretion, some patients develop frank diabetes mellitus that does not respond adequately to insulin therapy. Insulinlike growth factor I exerts metabolic effects similar to those of insulin. This study assessed the potential effectiveness of IGF-I as a blood glucose lowering agent in patients with extreme insulin resistance syndromes, including type A insulin resistance, congenital generalized lipodystrophy, and leprechaunism. Among the 11 patients studied, some exhibited mutated insulin receptors, whereas others were suspected to have defects in postreceptor sites. In each patient, plasma glucose levels decreased in response to subcutaneous injections of recombinant human IGF-I (0.1-0.3 mg/kg body wt). The degree of the decrease was roughly comparable with that observed in normal individuals. IGF-I also reduced plasma insulin concentrations. A long-term trial of IGF-I (up to 16 mo) showed that IGF-I (0.1-0.4 mg/kg body wt twice daily) is effective in lowering both fasting and postprandial plasma glucose concentrations with decreases in both fructosamine and HbA1c values. Improvement of acanthosis nigricans was observed in some of the patients. These results suggest that recombinant human IGF-I could be used clinically as a hypoglycemic agent in diabetic patients with extreme insulin resistance in whom insulin treatment is ineffective.
Diabetes 1993 May
PMID:Trial of insulinlike growth factor I therapy for patients with extreme insulin resistance syndromes. 848 26

A 60-year-old woman with a progressive virilization for about 5 yr developed diabetes mellitus with elevated insulin levels (fasting insulinemia ranging 32.4-45.8 microU/ml). The marked increase of plasma testosterone (total 5.7-8.2 ng/ml; free 11.5 pg/ml) and other endocrine markers clearly indicated the ovarian origin of hyperandrogenism. Pelvic ultrasonography, computerized axial tomography, and direct examination of ovaries during laparotomy, showed no evidence of neoplasia. Microscopic examination and immunocytochemical investigations confirmed the diagnosis of hyperthecosis. After oophorectomy and regression of hyperandrogenism, fasting and postprandial blood glucose concentrations normalized in spite of persistently elevated levels of insulinemia (fasting values ranging 32.0-61.0 microU/ml). The present case suggests that pathological increase of testosterone can interfere with insulin-glucose balance impairing the peripheral sensitivity to insulin.
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PMID:Reduction of insulin resistance after correction of nonneoplastic ovarian virilization. 851 85

Three further cases of mature benign cystic teratomas of the ovary associated with virilization are added to the three previously reported in the literature. They were found in postmenopausal, obese, diabetic women aged 52, 61, and 67 years. The patients presented with hirsutism and voice changes and clitoromegaly was present in one. Testosterone and androstenedione levels were elevated but promptly regressed after removal of the tumours. Histologically, sheets of stromal luteinized cells were found peripherally at the interface between the neoplasm and ovarian tissue. Luteinization of ovarian stroma induced by an unknown factor related to diabetes mellitus is the origin of the virilization.
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PMID:Virilizing mature ovarian cystic teratomas. 929 97

The cardinal clinical features of PCOS are hirsutism and menstrual irregularity from anovulation. Obesity occurs in approximately 50% of hyperandrogenic anovulatory women, some of whom also have non-insulin-dependent diabetes mellitus. Underlying these clinical findings are several biochemical abnormalities, including LH hypersecretion, hyperandrogenism, acyclic estrogen production, decreased SHBG capacity, and hyperinsulinemia, all of which contribute to increased ovarian production of androgens, particularly T. A fundamental mechanism of ovarian hyperandrogenism in PCOS is LH hypersecretion. Whether the central nervous system is a possible locus for initiating LH hypersecretion remains unclear, because exaggerated LH secretion is temporarily reversed by induced ovulatory cycles or physiologic luteal concentrations of progesterone. On the other hand, desynchronization of pulsatile LH secretion from sleep in girls with PCOS and an exaggerated (e.g., masculinized) early LH response to GnRHa testing in women with hyperandrogenic anovulation and congenital adrenal virilizing disorders suggest that events occurring before puberty, perhaps during fetal life, may irreversibly alter neuroendocrine function. Hyperinsulinemia from insulin resistance is an important regulatory mechanism governing ovarian hyperandrogenism. Hyperinsulinemia in hyperandrogenic anovulatory women potentiates ovarian hyperandrogenism by enhancing LH secretion; potentiating 17-hydroxylase and, to a lesser extent, 17,20-lyase activity; and suppressing SHBG capacity. It is a key component of hyperandrogenic anovulation caused by a type of insulin resistance that in independent and additive to that of obesity alone. Although the mechanisms governing insulin action on ovarian steroidogenesis are unknown, abnormalities of intracellular insulin signaling or cytochrome P450c 17[alpha] activity may render the 17-hydroxylase/17,20-lyase enzyme complex more sensitive to insulin. Hyperinsulinemia in hyperandrogenic anovulatory women is accompanied by upper-body obesity characterized by an increased amount of abdominal fat. Upper-body obesity is an important independent risk factor for CVD and diabetes. Although genetic and environmental factors affect fat distribution, sex steroids, particularly androgens, regulate lipid metabolism, suggesting yet another link between the hormonal and metabolic abnormalities of hyperandrogenic anovulation. A careful history and physical examination guide the extent of diagnostic testing. Slowly progressive hirsutism with anovulation of peripubertal onset usually reflects hyperandrogenic anovulation. This type of clinical presentation requires an evaluation to rule out other endocrinopathies (e.g., virilizing tumors, adult-onset CAH, hyperprolactinemia, and Cushing's syndrome). Virilization or severe rapidly progressive hirsutism requires immediate investigation to rule out a possible virilizing tumor. The ultimate goals of therapy for hyperandrogenic anovulatory women are to normalize the endometrium, antagonize androgen action at target tissues, reduce insulin resistance, and correct anovulation, if necessary.
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PMID:Polycystic ovary syndrome. 942 64

Congenital lipodystrophy is an uncommon autosomal recessive disorder that occurs mainly in females and is characterized by loss of subcutaneous fat, insulin-dependent diabetes mellitus, and masculinization due to defective metabolism of fat. Acquired lipodystrophy is now most commonly encountered in patients infected with HIV who take protease inhibitors. We present an illustrative case of lipodystrophy and review the presenting signs allowing for an accurate clinical diagnosis.
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PMID:Lipodystrophy. 1123 28

Genetic defects in genes encoding hormones, hormone receptors or polypeptides of the signaling pathways usually cause complex disease manifestations characterized by the involvement of several tissues and variable expression. Genetic aberrations, like chromosome aneuploidy, gene translocations or mutations in key regulatory proteins (even if not directly affecting genes of the endocrine system) often lead to clinical symptoms, including central endocrine functions like sexual differentiation or metabolic disturbances, like diabetes mellitus. But also minor genetic alterations like point mutations can affect the function of gene products to cause endocrine diseases. If the underlying molecular defects of endocrinopathies are known, direct molecular diagnosis can be performed. This is particularly useful if it helps to solve difficult differential diagnosis problems or if there exist effective preventive therapeutic options. The present paper presents examples for endocrine diseases in which molecular testing significantly increases the specificity and sensitivity of diagnostics and demonstrates the benefits for the patients and the healthcare system. In multiple endocrine neoplasia type 2, an unambiguous identification of gene carriers in affected families can be achieved by genetic testing. As a preventive measure to avoid medullary thyroid carcinoma, prophylactic thyroidectomy is recommended for individuals carrying the disease causing mutation. In adrenogenital syndrome, sequence analysis of the steroid 21-hydroxylase gene has become an important tool to confirm or exclude suspected late-onset forms of the disease, where hormone measurements are not informative. The major benefit, however, lies in identifying heterozygous carriers and providing a reliable prenatal test for couples carrying a defect in the 21-hydroxylase gene. Today, prenatal treatment with dexamethasone, which prevents the virilization in female fetuses, should always be based on results from molecular diagnosis performed from chorionic villus samples.
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PMID:Clinical impact of molecular diagnostics in endocrinology. Polymorphisms, mutations and DNA technologies. 1243 89

Dermatologists may commonly see skin lesions that reflect an underlying endocrine disorder. Identifying the endocrinopathy is very important, so that patients can receive corrective rather than symptomatic treatment. Skin diseases with underlying endocrine pathology include: thyrotoxicosis; hypothyroidism; Cushing syndrome; Addison disease; acromegaly; hyperandrogenism; hypopituitarism; primary hyperparathyroidism; hypoparathyroidism; pseudohypoparathyroidism and manifestations of diabetes mellitus. Thyrotoxicosis may lead to multiple cutaneous manifestations, including hair loss, pretibial myxedema, onycholysis and acropachy. In patients with hypothyroidism, there is hair loss, the skin is cold and pale, with myxedematous changes, mainly in the hands and in the periorbital region. The striking features of Cushing syndrome are centripetal obesity, moon facies, buffalo hump, supraclavicular fat pads, and abdominal striae. In Addison disease, the skin is hyperpigmented, mostly on the face, neck and back of the hands. Virtually all patients with acromegaly have acral and soft tissue overgrowth, with characteristic findings, like macrognathia and enlarged hands and feet. The skin is thickened, and facial features are coarser. Conditions leading to hyperandrogenism in females present as acne, hirsutism and signs of virilization (temporal balding, clitoromegaly).A prominent feature of hypopituitarism is a pallor of the skin with a yellowish tinge. The skin is also thinner, resulting in fine wrinkling around the eyes and mouth, making the patient look older. Primary hyperparathyroidism is rarely associated with pruritus and chronic urticaria. In hypoparathyroidism, the skin is dry, scaly and puffy. Nails become brittle and hair is coarse and sparse. Pseudohypoparathyroidism may have a special somatic phenotype known as Albright osteodystrophy. This consists of short stature, short neck, brachydactyly and subcutaneous calcifications. Some of the cutaneous manifestations of diabetes mellitus include necrobiosis lipoidica diabeticorum, diabetic dermopathy, scleredema adultorum and acanthosis nigricans.
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PMID:Cutaneous manifestations of endocrine disorders: a guide for dermatologists. 1268 37

Acne and body hair are both cutaneous responses to androgenic stimulation. They are normal events in adolescent girls. There is considerable variation in the evolution of the two conditions. The sebaceous gland is exquisitely sensitive to androgens, and acne appears with the onset of puberty, peaks in prevalence in the teenage years and gradually improves thereafter. Hair growth on the face, trunk and limbs develops more slowly and generally peaks in the 20s. Indications for endocrine investigation include very severe acne, onset of acne and hirsuties in the very early stage of puberty (Tanner stage 3) and systemic virilism. Treatment for acne and hirsuties can be either topical or systemic. The choice of therapy is based on the severity of the disease rather than the results of endocrine investigation. Further, since PCO is related to impaired glucose tolerance, advice relating to lifestyle changes should be offered to prevent the development of diabetes.
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PMID:Acne and hirsuties in teenagers. 1275 31


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