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

The 825T allele of the gene GNB3 which encodes the beta 3 subunit of heterotrimeric G proteins is associated with enhanced signal transduction via G proteins through the generation of a splice variant termed Gbeta3s. It was detected following a classical candidate gene approach using cell lines from patients with enhanced signal transduction and essential hypertension. The high frequency of the 825T allele in 'old' ethnicities, e.g. bushmen and Australian aborigines as well as in black populations, together with its strong association with obesity suggests that the 825T allele is a true 'thrifty genotype'. Development of obesity associated with the 825T allele is strongly influenced by lifestyle, e.g. physical activity, and other exogenous influences like pregnancy. In hypertension the 825T allele is associated with low renin activity and appears to strongly predict the development of left ventricular hypertrophy. In type 2 diabetes the 825T allele was reported to be predispose for end-stage renal disease, whereas this effect has not yet been confirmed for patients with type 1 diabetes.
Nephrol Dial Transplant 2000 Sep
PMID:G protein beta 3 subunit 825T allele, hypertension, obesity, and diabetic nephropathy. 1139 Jul 42

The prevalence of type 2 diabetes is rising in all Westernized societies. Presumably as a consequence of diminishing cardiovascular mortality, end-stage renal failure (ESRF) in patients with diabetes (mostly type 2) as a co-morbid condition has risen dramatically in the past decade. This constellation has become the single most common cause of ESRF in most countries. Such an epidemiological trend is particularly regrettable, since in uraemic diabetic patients, medical rehabilitation and survival are remarkably poor. Recent studies indicate that an interplay between genetic predisposition and factors, some of them susceptible to intervention, such as hyperglycaemia, blood pressure, smoking, age, gender and ethnicity, predispose to the development and progression of nephropathy. It has also become clear that trace albuminuria ('microalbuminuria') provides unique opportunities to recognize incipient renal involvement early on, although it is less specific in type 2 as compared with type 1 diabetes. Factors that promote progression include hypertension, proteinuria, smoking, glycaemic control and, less certainly, dietary protein intake and hyperlipidaemia. Cumulating evidence indicates that early intervention delays progression of nephropathy. The most important strategies to combat the medical catastrophe of increasing numbers of diabetic patients with ESRF include: (i) prevention of diabetes (mainly type 2); (ii) glycaemic control to prevent onset of renal involvement; and (iii) meticulous antihypertensive treatment to avoid progression of nephropathy.
Nephrol Dial Transplant 2001
PMID:Renal disease in type 2 diabetes. 1150 79

Diabetes complicating pregnancy has not yet been properly evaluated in Guam and the prevalence and morbidity of infants of diabetic mothers (IDM) in Micronesian population on Guam is described. The prevalence of IDM among the Micronesian population is 5.0% vs non-Micronesian's 3.7%. 82.5% were gestational diabetic mothers (GDM) diet controlled, 10.2% were GDM insulin controlled and 6.9% had Insulin Dependent Diabetes Mellitus. LGAs were 11% of IDMs in contrast to 6.4% of total births. Ten infants (NICU) spent total of 29 days on ventilator. Cesarean delivery, LGA, oxygen and ventilatory requirements were higher in Micronesian IDMs than in the non-Micronesian IDMs. The incidence is also higher in the Micronesian population (5.0%) compared to non Micronesian population (3.7%) on Guam. Micronesian IDMs were at higher risk for cesarean delivery, recurrent hypoglycemia, oxygen and ventilatory requirements than their non-Micronesian counterparts were. There is also a higher incidence of LGA among the Micronesian population and Chuukese had the highest incidence probably because they seek late or no prenatal care. We report 5.0% prevalence of diabetes during pregnancy in Micronesian population on Guam which imposes a significant economic burden on the local government's hospital resources. Micronesian IDMs were at higher risk for cesarean delivery, LGA, recurrent hypoglycemia, oxygen and ventilatory requirements than their non-Micronesian counterparts were. Chuukese had the highest LGA incidence in the study group. About 2/3rd of the IDM stayed 1110 extra days in hospital. IDMs accounted for the majority of expensive off-island transports.
Pac Health Dialog 2002 Sep
PMID:Epidemiology of infants of diabetic mothers in indigent Micronesian population-Guam experience. 1473 4

Diabetic kidney disease (DKD) is a common complication of type 1 diabetes (T1D) and a major risk factor for premature death from cardiovascular disease (CVD). Current treatments, such as control of hyperglycaemia and hypertension, are beneficial, but only partially protect against DKD. Finding new, safe and effective therapies to halt nephropathy progression has proven to be challenging. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated, in addition to glycaemic lowering, impressive protection against DKD and CVD progression in people with type 2 diabetes. Although these beneficial cardiorenal effects may also apply to people with T1D, supporting data are lacking. Furthermore, the increased rates of euglycaemic diabetic ketoacidosis may limit the use of this class in people with T1D. In this review we highlight the pathophysiology of DKD in T1D and the unmet need that exists. We further detail the beneficial and adverse effects of SGLT2 inhibitors based on their mechanism of action. Finally, we balance the effects in people with T1D and indicate future lines of research.
Nephrol Dial Transplant 2020 01 01
PMID:Role of sodium-glucose cotransporter 2 inhibition to mitigate diabetic kidney disease risk in type 1 diabetes. 3200 32

The rationale for using sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) has evolved over the last decade. Due to the effects on glucosuria and body weight loss, SGLT2 inhibitors were originally approved for glycemic control in T2D. Since glucosuria is attenuated in chronic kidney disease (CKD) Stages 3-5, initial regulatory approval for SGLT2 inhibitor use was limited to patients with T2D and preserved estimated glomerular filtration rate. Over time, however, it has become increasingly apparent that these therapies have a variety of important pharmacodynamic and clinical effects beyond glycemic lowering, including antihypertensive and antialbuminuric properties, and the ability to reduce glomerular hypertension. Importantly, these sodium-related effects are preserved across CKD stages, despite attenuated glycemic effects, which are lost at CKD Stage 4. With the completion of cardiovascular (CV) outcome safety trials-EMPA-REG OUTCOME, CANVAS Program and DECLARE TIMI-58-in addition to reductions in CV events, SGLT2 inhibition consistently reduces hard renal endpoints. Importantly, these CV and renal effects are independent of glycemic control. Subsequent data from the recent CREDENCE trial-the first dedicated renal protection trial with SGLT-2 inhibition-demonstrated renal and CV benefits in albuminuric T2D patients, pivotal results that have expanded the clinical importance of these therapies. Ongoing trials will ultimately determine whether SGLT2 inhibition will have a role in renal protection in other clinical settings, including nondiabetic CKD and type 1 diabetes.
Nephrol Dial Transplant 2020 01 01
PMID:Renal physiology of glucose handling and therapeutic implications. 3200 35


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