Abstract
12 identical twin pairs discordant for non-insulin-dependent diabetes mellitus (NIDDM) were studied for insulin sensitivity (euglycemic insulin clamp, 40 mU/m2 per min), hepatic glucose production (HGP, [3-3H]glucose infusion), and insulin secretion (oral glucose tolerance test and hyperglycemic [12 mM] clamp, including glucagon administration). Five of the nondiabetic twins had normal and seven had impaired glucose tolerance. 13 matched, healthy subjects without a family history of diabetes were included as control subjects. The NIDDM twins were more obese compared with their non-diabetic co-twins. The nondiabetic twins were insulin resistant and had a delayed insulin and C-peptide response during oral glucose tolerance tests compared with controls. Furthermore, the nondiabetic twins had a decreased first-phase insulin response and a decreased maximal insulin secretion capacity during hyperglycemic clamping and intravenous glucagon administration. Nondiabetic twins and controls had similar rates of HGP. Compared with both nondiabetic twins and controls, the NIDDM twins had an elevated basal rate of HGP, a further decreased insulin sensitivity, and a further impaired insulin secretion pattern as determined by all tests. In conclusion, defects of both in vivo insulin secretion and insulin action are present in non- and possibly prediabetic twins who possess the necessary NIDDM susceptibility genes. However, all defects of both insulin secretion and glucose metabolism are expressed quantitatively more severely in their identical co-twins with overt NIDDM.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barnett A. H., Eff C., Leslie R. D., Pyke D. A. Diabetes in identical twins. A study of 200 pairs. Diabetologia. 1981 Feb;20(2):87–93. doi: 10.1007/BF00262007. [DOI] [PubMed] [Google Scholar]
- Barnett A. H., Spiliopoulos A. J., Pyke D. A., Stubbs W. A., Burrin J., Alberti K. G. Metabolic studies in unaffected co-twins of non-insulin-dependent diabetics. Br Med J (Clin Res Ed) 1981 May 23;282(6277):1656–1658. doi: 10.1136/bmj.282.6277.1656. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bodkin N. L., Metzger B. L., Hansen B. C. Hepatic glucose production and insulin sensitivity preceding diabetes in monkeys. Am J Physiol. 1989 May;256(5 Pt 1):E676–E681. doi: 10.1152/ajpendo.1989.256.5.E676. [DOI] [PubMed] [Google Scholar]
- CERASI E., LUFT R. PLASMA-INSULIN RESPONSE TO SUSTAINED HYPERGLYCEMIA INDUCED BY GLUCOSE INFUSION IN HUMAN SUBJECTS. Lancet. 1963 Dec 28;2(7322):1359–1361. doi: 10.1016/s0140-6736(63)90740-2. [DOI] [PubMed] [Google Scholar]
- Colwell J. A., Lein A. Diminished insulin response to hyperglycemia in prediabetes and diabetes. Diabetes. 1967 Aug;16(8):560–565. doi: 10.2337/diab.16.8.560. [DOI] [PubMed] [Google Scholar]
- Cowan J. S., Hetenyi G., Jr Glucoregulatory responses in normal and diabetic dogs recorded by a new tracer method. Metabolism. 1971 Apr;20(4):360–372. doi: 10.1016/0026-0495(71)90098-9. [DOI] [PubMed] [Google Scholar]
- DeFronzo R. A. Pathogenesis of type 2 (non-insulin dependent) diabetes mellitus: a balanced overview. Diabetologia. 1992 Apr;35(4):389–397. doi: 10.1007/BF00401208. [DOI] [PubMed] [Google Scholar]
- DeFronzo R. A., Tobin J. D., Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979 Sep;237(3):E214–E223. doi: 10.1152/ajpendo.1979.237.3.E214. [DOI] [PubMed] [Google Scholar]
- Eriksson J., Franssila-Kallunki A., Ekstrand A., Saloranta C., Widén E., Schalin C., Groop L. Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Engl J Med. 1989 Aug 10;321(6):337–343. doi: 10.1056/NEJM198908103210601. [DOI] [PubMed] [Google Scholar]
- Gerich J. E. Is muscle the major site of insulin resistance in type 2 (non-insulin-dependent) diabetes mellitus? Diabetologia. 1991 Aug;34(8):607–610. doi: 10.1007/BF00400282. [DOI] [PubMed] [Google Scholar]
- Gulli G., Ferrannini E., Stern M., Haffner S., DeFronzo R. A. The metabolic profile of NIDDM is fully established in glucose-tolerant offspring of two Mexican-American NIDDM parents. Diabetes. 1992 Dec;41(12):1575–1586. doi: 10.2337/diab.41.12.1575. [DOI] [PubMed] [Google Scholar]
- Haffner S. M., Stern M. P., Hazuda H. P., Mitchell B. D., Patterson J. K. Increased insulin concentrations in nondiabetic offspring of diabetic parents. N Engl J Med. 1988 Nov 17;319(20):1297–1301. doi: 10.1056/NEJM198811173192001. [DOI] [PubMed] [Google Scholar]
- Halter J. B., Graf R. J., Porte D., Jr Potentiation of insulin secretory responses by plasma glucose levels in man: evidence that hyperglycemia in diabetes compensates for imparied glucose potentiation. J Clin Endocrinol Metab. 1979 Jun;48(6):946–954. doi: 10.1210/jcem-48-6-946. [DOI] [PubMed] [Google Scholar]
- Hauge M., Harvald B., Fischer M., Gotlieb-Jensen K., Juel-Nielsen N., Raebild I., Shapiro R., Videbech T. The Danish twin register. Acta Genet Med Gemellol (Roma) 1968 Apr;17(2):315–332. doi: 10.1017/s1120962300012749. [DOI] [PubMed] [Google Scholar]
- Hemmilä I., Dakubu S., Mukkala V. M., Siitari H., Lövgren T. Europium as a label in time-resolved immunofluorometric assays. Anal Biochem. 1984 Mar;137(2):335–343. doi: 10.1016/0003-2697(84)90095-2. [DOI] [PubMed] [Google Scholar]
- Ho L. T., Chang Z. Y., Wang J. T., Li S. H., Liu Y. F., Chen Y. D., Reaven G. M. Insulin insensitivity in offspring of parents with type 2 diabetes mellitus. Diabet Med. 1990 Jan;7(1):31–34. doi: 10.1111/j.1464-5491.1990.tb01303.x. [DOI] [PubMed] [Google Scholar]
- Hother-Nielsen O., Beck-Nielsen H. On the determination of basal glucose production rate in patients with type 2 (non-insulin-dependent) diabetes mellitus using primed-continuous 3-3H-glucose infusion. Diabetologia. 1990 Oct;33(10):603–610. doi: 10.1007/BF00400204. [DOI] [PubMed] [Google Scholar]
- Husby H., Holm N. V., Gernow A., Thomsen S. G., Kock K., Gürtler H. Zygosity, placental membranes and Weinberg's rule in a Danish consecutive twin series. Acta Genet Med Gemellol (Roma) 1991;40(2):147–152. doi: 10.1017/s0001566000002579. [DOI] [PubMed] [Google Scholar]
- Laws A., Stefanick M. L., Reaven G. M. Insulin resistance and hypertriglyceridemia in nondiabetic relatives of patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1989 Aug;69(2):343–347. doi: 10.1210/jcem-69-2-343. [DOI] [PubMed] [Google Scholar]
- Leslie R. D., Volkmann H. P., Poncher M., Hanning I., Orskov H., Alberti K. G. Metabolic abnormalities in children of non-insulin dependent diabetics. Br Med J (Clin Res Ed) 1986 Oct 4;293(6551):840–842. doi: 10.1136/bmj.293.6551.840. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lillioja S., Mott D. M., Howard B. V., Bennett P. H., Yki-Järvinen H., Freymond D., Nyomba B. L., Zurlo F., Swinburn B., Bogardus C. Impaired glucose tolerance as a disorder of insulin action. Longitudinal and cross-sectional studies in Pima Indians. N Engl J Med. 1988 May 12;318(19):1217–1225. doi: 10.1056/NEJM198805123181901. [DOI] [PubMed] [Google Scholar]
- Lillioja S., Mott D. M., Spraul M., Ferraro R., Foley J. E., Ravussin E., Knowler W. C., Bennett P. H., Bogardus C. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. N Engl J Med. 1993 Dec 30;329(27):1988–1992. doi: 10.1056/NEJM199312303292703. [DOI] [PubMed] [Google Scholar]
- Lukaski H. C., Johnson P. E., Bolonchuk W. W., Lykken G. I. Assessment of fat-free mass using bioelectrical impedance measurements of the human body. Am J Clin Nutr. 1985 Apr;41(4):810–817. doi: 10.1093/ajcn/41.4.810. [DOI] [PubMed] [Google Scholar]
- Martin B. C., Warram J. H., Krolewski A. S., Bergman R. N., Soeldner J. S., Kahn C. R. Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet. 1992 Oct 17;340(8825):925–929. doi: 10.1016/0140-6736(92)92814-v. [DOI] [PubMed] [Google Scholar]
- McGuire E. A., Helderman J. H., Tobin J. D., Andres R., Berman M. Effects of arterial versus venous sampling on analysis of glucose kinetics in man. J Appl Physiol. 1976 Oct;41(4):565–573. doi: 10.1152/jappl.1976.41.4.565. [DOI] [PubMed] [Google Scholar]
- Mitrakou A., Kelley D., Mokan M., Veneman T., Pangburn T., Reilly J., Gerich J. Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. N Engl J Med. 1992 Jan 2;326(1):22–29. doi: 10.1056/NEJM199201023260104. [DOI] [PubMed] [Google Scholar]
- Molina J. M., Baron A. D., Edelman S. V., Brechtel G., Wallace P., Olefsky J. M. Use of a variable tracer infusion method to determine glucose turnover in humans. Am J Physiol. 1990 Jan;258(1 Pt 1):E16–E23. doi: 10.1152/ajpendo.1990.258.1.E16. [DOI] [PubMed] [Google Scholar]
- Newman B., Selby J. V., King M. C., Slemenda C., Fabsitz R., Friedman G. D. Concordance for type 2 (non-insulin-dependent) diabetes mellitus in male twins. Diabetologia. 1987 Oct;30(10):763–768. doi: 10.1007/BF00275741. [DOI] [PubMed] [Google Scholar]
- O'Rahilly S., Turner R. C., Matthews D. R. Impaired pulsatile secretion of insulin in relatives of patients with non-insulin-dependent diabetes. N Engl J Med. 1988 May 12;318(19):1225–1230. doi: 10.1056/NEJM198805123181902. [DOI] [PubMed] [Google Scholar]
- Osei K. Increased basal glucose production and utilization in nondiabetic first-degree relatives of patients with NIDDM. Diabetes. 1990 May;39(5):597–601. doi: 10.2337/diab.39.5.597. [DOI] [PubMed] [Google Scholar]
- Peiris A. N., Stagner J. I., Vogel R. L., Nakagawa A., Samols E. Body fat distribution and peripheral insulin sensitivity in healthy men: role of insulin pulsatility. J Clin Endocrinol Metab. 1992 Jul;75(1):290–294. doi: 10.1210/jcem.75.1.1619021. [DOI] [PubMed] [Google Scholar]
- Porte D., Jr Banting lecture 1990. Beta-cells in type II diabetes mellitus. Diabetes. 1991 Feb;40(2):166–180. doi: 10.2337/diab.40.2.166. [DOI] [PubMed] [Google Scholar]
- STEELE R. Influences of glucose loading and of injected insulin on hepatic glucose output. Ann N Y Acad Sci. 1959 Sep 25;82:420–430. doi: 10.1111/j.1749-6632.1959.tb44923.x. [DOI] [PubMed] [Google Scholar]
- Schumacher M. C., Maxwell T. M., Wu L. L., Hunt S. C., Williams R. R., Elbein S. C. Dyslipidemias among normoglycemic members of familial NIDDM pedigrees. Diabetes Care. 1992 Oct;15(10):1285–1289. doi: 10.2337/diacare.15.10.1285. [DOI] [PubMed] [Google Scholar]
- Soeldner J. S., Gleason R. E., Williams R. F., Garcia M. J., Beardwood D. M., Marble A. Diminished serum insulin response to glucose in genetic prediabetic males with normal glucose tolerance. Diabetes. 1968 Jan;17(1):17–26. doi: 10.2337/diab.17.1.17. [DOI] [PubMed] [Google Scholar]
- Vaag A., Damsbo P., Hother-Nielsen O., Beck-Nielsen H. Hyperglycaemia compensates for the defects in insulin-mediated glucose metabolism and in the activation of glycogen synthase in the skeletal muscle of patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 1992 Jan;35(1):80–88. doi: 10.1007/BF00400856. [DOI] [PubMed] [Google Scholar]
- Vaag A., Henriksen J. E., Beck-Nielsen H. Decreased insulin activation of glycogen synthase in skeletal muscles in young nonobese Caucasian first-degree relatives of patients with non-insulin-dependent diabetes mellitus. J Clin Invest. 1992 Mar;89(3):782–788. doi: 10.1172/JCI115656. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Warram J. H., Martin B. C., Krolewski A. S., Soeldner J. S., Kahn C. R. Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Ann Intern Med. 1990 Dec 15;113(12):909–915. doi: 10.7326/0003-4819-113-12-909. [DOI] [PubMed] [Google Scholar]
- Yki-Järvinen H. Pathogenesis of non-insulin-dependent diabetes mellitus. Lancet. 1994 Jan 8;343(8889):91–95. doi: 10.1016/s0140-6736(94)90821-4. [DOI] [PubMed] [Google Scholar]
- Zimmet P. Type 2 (non-insulin-dependent) diabetes--an epidemiological overview. Diabetologia. 1982 Jun;22(6):399–411. doi: 10.1007/BF00282581. [DOI] [PubMed] [Google Scholar]