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Query: UMLS:C0011854 (type 1 diabetes)
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A remarkably coordinated set of metabolic adaptations allows the intermittently feeding mother to provide not only for her own energy needs, but also for those of the continuously feeding and developing fetus. During feeding, progressive insulin resistance and compensatory hyperinsulinemia appear to promote storage of nutrients in maternal fat and serve to "shunt" nutrients to the fetus by slowing their uptake into maternal tissues, especially during late pregnancy. Between feedings, hormones liberated by the fetoplacental unit create an environment that progressively favors maternal fat catabolism as an energy substrate source, thus curbing maternal protein catabolism while keeping some carbohydrate available for the fetus. These normal changes have important implications for women with abnormal glucoregulation. Women with pre-gestational diabetes will need progressively greater insulin doses during gestation in order to maintain normoglycemia and, in the case of women with IDDM, to avoid ketosis. Women without known diabetes may develop glucose intolerance by late gestation if their pancreatic B cells are not capable of compensating for their inherent insulin resistance and/or the normal insulin resistance of pregnancy. Norbert Freinkel was a leader in the development of our current physiological understanding of these metabolic adaptations to pregnancy. That understanding has contributed greatly to the improved outcome of pregnancies complicated by maternal diabetes. A major challenge for present and future investigators will be to develop an understanding of those adaptations at the molecular and genetic levels so that we may have even greater impact on the well-being of diabetic women and their offspring.
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PMID:Glucose metabolism during pregnancy: normal physiology and implications for diabetes mellitus. 196 41

In order to study the capacity of the first phase insulin response (FPIR) for predicting insulin-dependent diabetes (IDDM), we have performed one or more intravenous glucose tolerance tests (IVGTT) and determined islet-cell antibodies (ICA) and HLA-types in 220 first degree relatives of IDDM patients (194 siblings, 26 offsprings) aged 2 to 29 years. They were prospectively followed for periods ranging from 18 months to 8 years. The immunological and metabolic changes in 9 subjects who have developed IDDM or impaired glucose tolerance during the study and in 3 ICA-positive non-diabetic subjects were compared to those in ICA-negative subjects. Although the mean FPIR (1 + 3 min. plasma insulin) was significantly lower in ICA-positive compared with ICA-negative subjects, a unique low FPIR had no predictive value at the individual level. At repeated tests, the two groups followed distinctive evolutive patterns: ICA-negative subjects usually had higher FPIRs at a 2nd test, while FPIRs remained low or still decreased in ICA-positive subjects. Follow-up of subjects at high risk showed good concordance between the different predictive factors: among the 9 subjects who have developed IDDM, 7 had persisting ICA, 8 were HLA-DR3, DR4; the FPIR was consistently low in 3 and low at least once in 4. Progressive loss of the FPIR allowing to predict the time of onset of IDDM, was not observed.
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PMID:[Decrease of early insulin secretion, risk factor of insulin-dependent diabetes. Prospective study in families with diabetic children]. 201 14

A study was made of glucose tolerance and insulin secretion in 33 persons who later developed insulin-dependent diabetes (aged 4-24 years) and observation continued further in the first years after manifestation. Patients who developed the typical labile type of diabetes were of normal weight and had either normal glucose tolerance tests before diagnosis or had impaired glucose tolerance (IGT) for a short interval of 2-16 months. Subjects with IGT over a significantly (p less than 0.01) longer period of 32.30 +/- 6.25 (normal body weight) or 94.71 +/- 20.62 (obese) months developed a milder form of diabetes with retarded insulin dependency in obese subjects. The severe and mild form of IDDM are distinct with respect to insulin requirement (0.75 +/- 0.03 or 0.28 +/- 0.04 U/kg b.w., P less than 0.01) and glucagon stimulated C-peptide (0.18 +/- 0.05 or 1.41 +/- 0.27, P less than 0.01) in the first 2.5-3.5 years after onset. The two forms were not different regarding HLA-DR antigens. Islet cell surface antibodies investigated in 15 probands at 27 occasions before diabetes onset had no prognostic value. The development of a mild form of IDDM may be expected in cases with pre-existing IGT for more than one year. The insulin secretion is of low predictive value under these conditions. The observation is of practical use and theoretical interest.
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PMID:Glucose tolerance behaviour before the onset of type I (insulin-dependent) diabetes in young people as a predictor of the further course of the disease: a retrospective analysis of 33 cases. 202 75

Fifteen women with positive islet cell antibodies were identified in a group of 115 consecutive patients found to have impaired glucose tolerance in pregnancy. These subjects were postulated to be at increased risk of later developing type 1 diabetes mellitus. They were examined post--partum for HLA types known to be associated with this disease and for any increase in Interleukin 2 receptor expression or alteration of T cell subsets of possible relevance to its pathogenesis. Fifteen women negative for islet antibodies and with normal glucose tolerance during previous pregnancy and 15 women with a normal fasting plasma glucose who had never been pregnant were studied as controls. Using flow cytometric techniques a significant increase in both the number and proportion of activated (Interleukin 2 receptor, CD25) lymphocytes in the peripheral blood of women who had islet cell antibodies and previous impaired glucose tolerance in pregnancy was found (0.14 +/- SE 0.03 x 10(9)/l; 7.1 +/- 1.1%) when compared with normal parous controls (0.09 +/- 0.01 x 10(9)/l; 4.2 +/- 0.6%), p less than 0.01 x 10(9)/l; showed significant increases when compared with nulliparous controls (0.04 +/- 0.01 x 10(9)/l; 2.1 +/- 0.2%), p less than 0.01. No differences were detected between the three groups with respect to total T-lymphocytes (CD3), helper T-lymphocytes (CD4), suppressor cytotoxic T-lymphocytes (CD8), or the inducer of suppressor (Leu 3+/Leu 8+) subset of T-lymphocytes. Three women persistently islet cell antibody positive, two of whom were HLA DR4, showed impaired glucose tolerance at the time of lymphocyte subset analysis, while two further patients, one DR3 and the other DR4, had developed type 1 (insulin-dependent) diabetes. No correlation between increased Interleukin 2 receptor expression and glucose intolerance was demonstrated. We conclude that islet cell antibody positive women with impaired glucose tolerance during pregnancy are at increased risk of later developing type 1 diabetes but that heightened immune activation present in these women is in part a post-pregnancy phenomenon.
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PMID:Increased interleukin 2 receptor expression in post-gestational women: relationship to impaired glucose tolerance and islet cell antibodies in pregnancy. 210 86

The mean additional energy requirement for pregnancy has been calculated at 285 kcal daily and it reflects the energy needs for production of the fetoplacental unit and for the maternal physiological adaptations to pregnancy. In practice there is considerable variation in energy requirement due to alterations in maternal energy expenditure. Optimal energy intakes are dictated also by the pre-pregnancy maternal weight. The outcome of pregnancy is improved in the underweight mother by an intake which produces a weight gain in pregnancy of approximately 14 kg, whereas a rise of only 7 kg may be optimal for the obese mother. Obesity with or without diabetes is associated with macrosomia and other problems and it is sensible to attempt to limit weight gain in pregnancy at a time when maternal motivation is high. Diabetes in pregnancy may arise in patients with pre-existing NIDDM or IDDM, but more commonly it is diagnosed for the first time during pregnancy and it usually disappears after delivery (gestational diabetes). Recent evidence suggests that gestational diabetes has a strong genetic component and is usually NIDDM precipitated early in life by the pregnancy. Both gestational diabetes and NIDDM are characterized by insulin deficiency and by insulin resistance. Long-term follow-up studies have demonstrated that NIDDM or impaired glucose tolerance develop in later life in 50-70% of women with previous gestational diabetes. The adverse effects of pregnancy on the mother with pre-existing diabetes may be minimized by good diabetic control as may be adverse effects on the fetus and neonate of diabetes in the mother. An increased incidence of fetal malformations persists in pregnancies with pre-existing maternal diabetes. Diabetes of any form may be associated with neonatal hypoglycaemia. The aim of therapy is to produce maternal normoglycaemia throughout pregnancy by dietary measures and insulin treatment if required. Women with pre-existing diabetes should tighten their blood glucose control from before conception. Optimization of insulin therapy and diet are required for IDDM and most NIDDM women will require insulin treatment in pregnancy. Gestational diabetics require diet and possibly insulin. Most pregnancies now proceed to term.
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PMID:Diabetes and diet in pregnancy. 224 97

Forty-nine patients with tropical calcific pancreatitis (TCP), 51 insulin-dependent diabetics (IDDMs), 87 non-insulin-dependent diabetics (NID-DMs), and 66 nondiabetic controls were studied to evaluate their exocrine pancreatic function by measurement of serum immunoreactive trypsin (IRT, normal for white caucasians from the U.K. of 140-414 micrograms/L), pancreatic isoamylase (PIA, normal of 35-125 U/L), and fecal chymotrypsin (FCT, normal of greater than 6.6 u/g). The majority of patients were studied within 1 year of diagnosis. TCP subjects included 7 nondiabetics, 6 with impaired glucose tolerance (IGT-TCP), and 36 diabetics [fibrocalculous pancreatic diabetes (FCPD)]. There was evidence of active pancreatitis (IRT greater than 800 micrograms/L) and partial preservation of function in nondiabetic TCP subjects [median IRT of 220 micrograms/L (range of 102-1,360 micrograms/L), FCT of 2.2 u/g (range 0.7-12.8 u/g)] and also in IGT-TCP subjects [IRT of 370 micrograms/L (range of 30-1,360 micrograms/L), FCT of 4.2 u/g (range of 1-38 u/g)]. FCPDs showed severely diminished exocrine function [IRT of 50 micrograms/L (range of 0-184 micrograms/L), FCT of 0.23 u/g (range of 0-10.4 u/g)]; none showed IRT greater than 800 micrograms/L. IDDMs and NIDDMs also showed diminished exocrine pancreatic function in approximately 30 and approximately 10%, respectively. Controls showed a wide range of IRT and FCT concentrations; IRT concentrations tended to be higher than those reported in white Caucasians from the U.K. Three controls, one IDDM, and two NIDDMs showed "pancreatic" IRT concentrations in the absence of symptoms. PIA concentrations were diminished in FCPD but were similar in IDDM and NIDDM subjects compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exocrine pancreatic function (serum immunoreactive trypsin, fecal chymotrypsin, and pancreatic isoamylase) in Indian diabetics. 228 Oct 79

The author investigated in a long term study of 8.7 +/- +/- 3.9 years risk factors of atherosclerosis (RFA) in 70 offspring of both parents suffering from non-insulin-dependent diabetes. Their mean age at the onset of the investigation was 35.2 +/- 7.4 years. The author assessed the incidence of obesity, hypertension, hyperglycaemia and hyperinsulinaemia after oGTT, elevated levels of cholesterol, triglycerides, fibrinogen and a reduced ratio of HDL on electrophoresis. As risk factors they considered: Broca's index above 110%, blood pressure above 150/90 mm Hg and other values above the average + 2SD recorded in a control group of 33 healthy non-obese subjects without a diabetic family-history; HDL values lower than the mean--2SD of controls. During the investigation period the incidence of obesity increased significantly (P less than 0.01); of hypertension (P less than 0.01); hyperglycaemia (P less than 0.05); hyperinsulinaemia (P less than 0.001) and the incidence of a low HDL ratio (P less than 0.01). The mean RFA values were lowest in offspring with a normal oGTT, higher in liminal glucose tolerance and highest in impaired glucose tolerance and diabetes. The most important RFA include an elevated fibrinogen level. The results indicate that in subjects with a high genetic risk of the development of non-insulin dependent diabetes already in the earliest stage conditions for the development of atherosclerosis are present.
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PMID:[Risk factors for atherosclerosis in the early stages of diabetes]. 233 28

The hormonal and glycaemic responses to serial test meals have been well documented in normal subjects and in patients with insulin dependent diabetes. There is less information in patients with non-insulin dependent diabetes. We studied 39 newly diagnosed previously untreated non-insulin dependent diabetics. Each patient received four identical test meals over a 24 hour period and their plasma glucose and insulin levels were determined at frequent intervals throughout the study period. The results show that all the non-insulin dependent patients at diagnosis had large post-prandial glucose excursions, and that the post-prandial rise in insulin was delayed. The study also demonstrates that glucose and insulin profiles are dependent on the degree of obesity of the patient. Patients with non-insulin dependent diabetes have a greater degree of glucose intolerance in the morning in contrast to normal subjects whose glucose tolerance is best in the morning.
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PMID:Hormonal and glycaemic responses to serial meals in newly diagnosed non insulin dependent diabetic patients. 265 28

At the University of Iowa, Iowa City, 75 pancreas transplant procedures were performed for type I diabetes mellitus from March 1984 to September 1988. Forty-seven of these transplants were performed simultaneously with kidney transplants from the same donor; 23 followed previous kidney transplants, and 5 were preuremic pancreas-only transplants. The 1-year patient survival rate is 85% and pancreas graft survival rate is 54%. The simultaneous kidney and pancrease group had a 1-year patient survival rate of 82%, a pancreas graft survival rate of 59%, and a renal graft survival rate of 73%. Thirty-one of 70 kidney and pancreas recipients had a functioning pancreas 1 year post transplantation and 26 of 31 currently have a functioning pancreas and are insulin free. Patient symptoms of neuropathy and gastroenteropathy are improved with long-term graft function. Some patients may develop type II diabetes post transplantation with impaired glucose tolerance despite high insulin production by the graft. Pancreas transplantation is the only therapy that achieves a euglycemic state as indicated by glycosylated hemoglobin and glucose tolerance testing. Centers must continue to follow up patients on a long-term basis to determine the final effects on the secondary complications of diabetes.
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PMID:Function of pancreas allografts more than 1 year following transplantation. 266 39

Nineteen diabetics aged 9 to 18 years with the MODY type were investigated, incl. their families, by the oGTT. Diabetes in the parents was nine times and in siblings four times more frequent than in families of adolescents with IDDM. In parents the manifest form predominated, in siblings PGT. Vertical transmission of diabetes in three consecutive generations was found only in the MODY type (in 35%). Diabetes with the MODY type and their diabetic siblings did not differ significantly as to their mild glucose intolerance (blood sugar level up to 13 mmol/l), and their mild diabetic phenotypes did not differ either. Similarly diabetics with IDDM and their diabetic siblings did not differ substantially as to their severe glucose intolerance (blood sugar level up to 21 mmol/l), and their severe diabetic phenotypes did not differ either. IRI levels revealed five times a hyperinsulinaemic and three times a normal insulinaemic response. Obese diabetics were treated with a reducing diet and physical activity. To non-obese diabetics, if the above procedure was not sufficiently successful, sulphonylurea preparation were also administered. During check-up examinations fasting values and values three hours after a meal lower than 6.1 mmol/l were required. In the course of a four- to ten-year follow up it did not change. Existence of the MODY type already macroangiopathic complications developed; in one diabetic the glucose tolerance improved, in the remainder it did not change. Existence of the MODY type already in adolescents justifies early detection in families with a cumulated incidence of NIDDM and prophylactic procedures ensuring euglycaemia in confirmed diabetics.
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PMID:[MODY type diabetes mellitus in children and adolescents]. 275 88


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