c-peptide and Diseases-in-Twins

A 22-year-old Caucasian patient underwent living-donor liver transplantation (LDLT) for hepatic hemangioendothelioma in a healthy liver. The organ donor was his monozygotic twin brother. Surgery was uneventful in both donor and recipient, who received the same postoperative treatment (i.e. no immunosuppression for the recipient). Although both donor and recipient achieved a full liver function recovery, the volume of the recipient's graft increased much more than the donor's residual liver in the first postoperative month (1.6-fold vs. 1.2-fold). This different growth rate correlated with growth hormone (GH)/insulin growth factor (IGF) axis dynamics: the donor had significantly lower insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) values than the recipient on postoperative days (POD) 3-30, although they had similar GH values. Other potential regenerative factors, e.g. tumor necrosis alpha, interleukin 6 (IL-6), insulin and C peptide did not correlate with liver regeneration rate. The particular endocrine picture of the graft may be explained by a modified GH-hepatocyte interaction due to cold ischemia during preservation resulting in a higher IGF production. Whether this is a potential molecular tool by means of which transplanted partial livers promote their regeneration remains to be seen in a larger number of patients.

Topics: Adult; C-Peptide; Diseases in Twins; Growth Hormone; Hemangioendothelioma; Hepatocytes; Humans; Immunosuppressive Agents; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Interleukin-6; Kinetics; Liver; Liver Neoplasms; Liver Regeneration; Liver Transplantation; Living Donors; Male; Models, Statistical; Somatomedins; Time Factors; Transplantation, Isogeneic; Tumor Necrosis Factor-alpha; Twins, Monozygotic

Topics: Adolescent; Adult; Autoantibodies; Blood Glucose; C-Peptide; Cohort Studies; Diabetes Mellitus, Type 1; Diseases in Twins; Female; Glucose Intolerance; Humans; Hypoglycemia; Insulin; Longitudinal Studies; Self Administration; Time Factors; Twins, Monozygotic

Previous studies have demonstrated an association between low weight at birth and risk of later development of non-insulin-dependent diabetes mellitus (NIDDM). It is not known whether this association is due to an impact of intrauterine malnutrition per se, or whether it is due to a coincidence between the putative "NIDDM susceptibility genotype" and a genetically determined low weight at birth. It is also unclear whether differences in gestational age, maternal height, birth order and/or sex could explain the association. Twins are born of the same mother and have similar gestational ages. Furthermore, monozygotic (MZ) twins have identical genotypes. Original midwife birth weight record determinations were traced in MZ and dizygotic (DZ) twins discordant for NIDDM. Birth weights were lower in the NIDDM twins (n = 2 x 14) compared with both their identical (MZ; n = 14) and non-identical (DZ; n = 14) non-diabetic co-twins, respectively (MZ: mean +/- SEM 2634 +/- 135 vs 2829 +/- 131 g, p < 0.02; DZ: 2509 +/- 135 vs 2854 +/- 168 g, p < 0.02). Using a similar approach in 39 MZ and DZ twin pairs discordant for impaired glucose tolerance (IGT), no significantly lower birth weights were detected in the IGT twins compared with their normal glucose tolerant co-twins. However, when a larger group of twins with different glucose tolerance were considered, birth weights were lower in the twins with abnormal glucose tolerance (NIDDM + IGT; n = 106; 2622 +/- 45 g) and IGT (n = 62: 2613 +/- 55 g) compared with twins with normal glucose tolerance (n = 112: 2800 +/- 51 g; p = 0.01 and p = 0.03, respectively). Furthermore, the twins with the lowest birth weights among the two co-twins had the highest plasma glucose concentrations 120 min after the 75-g oral glucose load (n = 86 pairs: 9.6 +/- 0.6 vs 8.0 +/- 0.4 mmol/l, p = 0.03). In conclusion, the association between low birth weight and NIDDM in twins is at least partly independent of genotype and may be due to intrauterine malnutrition. IGT was also associated with low birth weight in twins. However, the possibility cannot be excluded that the association between low birth weight and IGT could be due to a coincidence with a certain genotype causing both low birth weight and IGT in some subjects.

Topics: Aged; Birth Order; Birth Weight; Blood Glucose; Body Height; C-Peptide; Cholesterol; Diabetes Mellitus, Type 2; Disease Susceptibility; Diseases in Twins; Female; Genomic Imprinting; Genotype; Glucose Tolerance Test; Humans; Infant, Low Birth Weight; Infant, Newborn; Insulin; Male; Middle Aged; Proinsulin; Sex Characteristics; Triglycerides; Twins, Dizygotic; Twins, Monozygotic

Intracellular glucose and lipid metabolism was studied in 12 identical twin pairs discordant for non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and 13 control subjects without family history of diabetes during low (baseline) and high plasma insulin concentrations, using the hyperinsulinaemic clamp technique combined with indirect calorimetry, tritiated water glycolytic flux rates and biopsy skeletal muscle glycogen synthase activity determinations. Baseline and insulin stimulated rates of lipid oxidation were elevated--and glucose oxidation decreased--in the NIDDM twins compared with the non-diabetic co-twins and controls (all p < 0.05). Baseline and insulin stimulated rates of glucose and lipid oxidation were similar in non-diabetic twins and controls. Exogenous glycolytic flux was decreased in NIDDM twins compared with both their non-diabetic co-twins and controls during clamp insulin measurements (p < 0.02), but similar in all study groups during baseline measurements. Insulin stimulated glucose disposal, exogenous glucose storage (glucose disposal-exogenous glycolytic flux) and skeletal muscle glycogen synthase activity were all significantly decreased in NIDDM twins compared with both their non-diabetic co-twins and controls. Furthermore, glucose disposal and glucose storage were decreased in the non-diabetic twins (n = 12) compared with controls (p < 0.05 both). However, insulin stimulated fractional skeletal muscle glycogen synthase activity was not significantly decreased in non-diabetic twins compared with controls.. (1) the glucose fatty acid cycle plays a major role in the secondary--but not the primary--abnormalities of glucose metabolism in NIDDM; (2) insulin resistance in non-diabetic identical co-twins of NIDDM patients is restricted exclusively to the pathway of exogenous glucose storage; (3) however, the decreased glucose storage is not explained solely by an impairment of insulin stimulated skeletal muscle glycogen synthase activity; and finally (4) the impairment of skeletal muscle glycogen synthase activity in NIDDM has an apparent non-genetic component and can be escaped (or postponed) in individuals (twins) with a 100% genetic predisposition to NIDDM.

Topics: Analysis of Variance; Biopsy; Blood Glucose; Body Mass Index; C-Peptide; Calorimetry, Indirect; Diabetes Mellitus, Type 2; Diseases in Twins; Fasting; Female; Glucose; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Infusions, Intravenous; Insulin; Male; Middle Aged; Muscle, Skeletal; Reference Values; Statistics, Nonparametric; Triglycerides; Twins, Monozygotic

Disproportionate elevation [increased proinsulin/insulin (PI/INS) ratio] of PI immunoreactivity is associated with noninsulin-dependent diabetes mellitus (NIDDM). The nature of this abnormality is not known. To address the question of whether genetic factors contribute to hyperproinsulinemia, we measured fasting levels of PI immunoreactivity, intact INS, and C peptide (CP) in 12 pairs of monozygotic twins discordant for NIDDM for a mean (+/- SEM) period of 9 +/- 3 yr. Thirteen age- and body mass index-matched healthy subjects without any family history of NIDDM acted as controls. The nondiabetic twins had levels of fasting INS, CP, PI, PI/CP, and PI/INS similar to those of control subjects. Fasting levels of PI, and PI/CP and PI/INS ratios were significantly 2- to 3-fold elevated in NIDDM twins compared to those in both nondiabetic twins and control subjects. To investigate whether hyperproinsulinemia in these NIDDM patients was due to a differential elevation of intact PI or conversion intermediates, we analyzed PI profiles in NIDDM twins and normal subjects by high pressure liquid chromatography. PI was heterogeneous and consisted mainly of des(31,32)-PI and intact PI in both NIDDM patients and normal subjects, with no major difference in composition between the groups. Small amounts of des(64,65)-PI (0-11%) were measured in some patients and normal subjects. The results suggest that hyperproinsulinemia is not a genetically determined trait per se in NIDDM. Disproportionately elevated PI levels seem to be related to the actual disease process. Further conversion of intact PI and des(31,32)-PI may be equally impaired in NIDDM.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Case-Control Studies; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 2; Diseases in Twins; Glucose Intolerance; Humans; Insulin; Proinsulin; Reference Values; Twins, Monozygotic

The B-cells of patients with recently diagnosed Type 1 (insulin-dependent) diabetes may have no response to glucose when the response to glucagon is present but attenuated. This observation suggests that the recognition of glucose is more severely affected than that for non-glucose stimulants. To determine whether a similar selective decrease in glucose response was present before the onset of diabetes we studied two groups of non-diabetic identical twins of patients with recently diagnosed Type 1 diabetes: one group with complement-fixing islet cell antibodies who were at high risk of developing diabetes (four of the five have already developed diabetes) and a group without such antibodies at low risk of developing diabetes. In addition, a group of patients with chronic pancreatitis were studied to control for non-specific damage to the B-cell. Responses to i.v. glucose and i.v. glucagon were compared. Patients with chronic pancreatitis has similar responses to both glucose and glucagon and the responses did not differ from control subjects. The B-cells of the immune positive group showed evidence of pathology because the insulin and C-peptide responses to both stimuli were reduced when compared to either their control subjects or the immune negative twin group. However, the B-cell response to both glucose and glucagon in the immune positive twins was similar. Because the B-cell response to glucose was not less than that to glucagon, a selective destruction of the glucose recognition system cannot be a characteristic of all twins throughout the period before they develop Type 1 diabetes.

Topics: Adult; Autoantibodies; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Diseases in Twins; Female; Glucagon; Glucose; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pancreatitis; Reference Values; Risk Factors; Twins, Monozygotic