Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes may be associated with many genetic disorders. The scientific importance of these often rare disorders resides in the insight they may provide into the possible mechanisms of common diabetes. The type of diabetes varies in these syndromes. Non-insulin-dependent diabetes (NIDDM), clinically similar to common NIDDM, may be found in some syndromes (e.g. Werner's syndrome). In others there may be considerable insulin resistance, such as that present in ataxia telangiectasia. Extreme insulin resistance due to abnormal insulin receptor function is found in the Mendenhall syndrome. The mechanism of diabetes is more obscure in acute intermittent porphyria (AIP), although haem deficiency affecting the cytochrome chain raises interesting possibilities. In glycogen storage disease type I, the diabetes is associated with insulinopenia, following an earlier period in the disease when hypoglycaemia is the rule. IDDM, clinically similar to the common form, is present in the autoimmune polyglandular syndromes. Although a change in the lean:fat ratio is common in many neuromuscular disorders, mechanisms other than insulin resistance would seem to operate. The increased incidence of diabetes in heterozygotes for some of these genetic disorders raises the possibility that many common diabetics are, in fact, heterozygotes for some other disorder. The increased frequency of diabetes in Klinefelter's syndrome, Turner's syndrome and possibly Down's syndrome leads to the hypothesis that non-disjunction may, in some way be associated with the predisposition to diabetes. In several syndromes there is an increased incidence of diabetes in otherwise unaffected relatives of individuals with these syndromes. It is impossible to assess what proportion of common NIDDM or IDDM is made up of heterozygotes for these genetic syndromes.
 ...
PMID:Diabetes secondary to genetic disorders. 144 74

A 12 year old Asian girl with a four year history of poorly controlled insulin dependent diabetes mellitus developed overt diabetic nephropathy. There were no clinical features of Rabson-Mendenhall syndrome. Screening for microalbuminuria would have identified incipient diabetic nephropathy and highlighted the importance of good glycaemic control. Although screening for microalbuminuria is recommended after five years from diagnosis, it may be appropriate to undertake this annually in those with poor glycaemic control.
 ...
PMID:Early onset of diabetic nephropathy. 949 90

Mutations in the insulin receptor gene cause the severe insulin-resistant syndromes leprechaunism and Rabson-Mendenhall syndrome, whose metabolic features include fasting hypoglycemia, post-prandial hyperglycemia, and extremely elevated insulin levels. Patients with Rabson-Mendenhall syndrome have a protracted course and eventually develop ketoacidosis. To determine the mechanism causing this progression and the paradoxical fasting hypoglycemia, we conducted a retrospective study in a patient with Rabson-Mendenhall syndrome, who was a compound heterozygous for two missense mutations affecting the kinase domain of the insulin receptor beta-subunit (I1115T and R1131W). At birth, the patient had fasting hypoglycemia and postprandial hyperglycemia. This was followed at approximately 3 yr of age by constant hyperglycemia and, at 6 yr of age, by constant ketoacidosis. Urinary organic acids during ketoacidosis resembled those of patients with type 1 diabetes. Plasma glucose levels increased (r2 = 0.31; P < 0.01), whereas insulin levels decreased with age (r2 = 0.51; P < 0.01). During periods ofhypoglycemia and hyperglycemia (0-1 yr of age), constant hyperglycemia (3-4 yr of age), and hyperglycemia with ketoacidosis (6-7 yr of age), insulin levels were significantly correlated with plasma glucose levels (P < 0.05). However, the slope of the regression and the predicted insulin level at zero glucose decreased with increasing age. When insulin levels were normalized for the plasma glucose concentrations, an exponential decrease in the insulin/glucose ratio was observed (r2 = 0.92; P < 0.01), with most of the decline occurring before 2 yr of age. These results indicate that the paradoxical fasting hypoglycemia of patients with Rabson-Mendenhall syndrome is associated with severely increased levels of circulating insulin and that the progression of this disease is due to a decline in insulin levels.
 ...
PMID:Progressive decline in insulin levels in Rabson-Mendenhall syndrome. 1044 50