DOI 10.15372/SSMJ20200113
CLINICAL FEATURES OF TYPE 2 DIABETES DIFFERENT PHENOTYPES
Author Affiliations1State Novosibirsk Regional Clinical Hospital 630087, Novosibirsk, Nemirovich-Danchenko str., 130
2Novosibirsk State Medical University of Minzdrav of Russia 630091, Novosibirsk, Krasny av., 52
Abstract
Objective of the study was to investigate clinical features of phenotypic variants of type 2 diabetes mellitus (T2DM) for personalization of hypoglycemic therapy. Material and methods. 2085 patients with T2DM (637 men and 1148 women), mean age 58.7 ± 6.9 years, duration of diabetes 7.8 ± 6.5 years; level of glycated hemoglobin (HbA1c), creatinine, urea, total cholesterol, triglycerides, low (LDL) and high density lipoprotein, uric acid, ALT, AST, insulin, C-peptide, microalbuminuria were examined. Depending on the level of C-peptide and the index of HOMA-IR, patients were divided into 3 groups: group of insulinopenic phenotype (n = 250, 12 %), group of classical phenotype (n = 1605, 77 %) and group of hyperinsulinemic phenotype (n = 230, 11 %). Results. Patients with hyperinsulinemic phenotype differed from patients with classical and insulinopenic phenotype by later age of onset of diabetes (52.3 ± 8.1 years), high body mass index (BMI; 37.2 ± 7.4 kg/m2), blood LDL (3.38 ± 1.08 mmol/l) and creatinine level and frequency of chronic kidney disease (39.1 %). Patients with the insulinopenic phenotype had less diabetes duration (48.3 ± 7.9 years), a lower BMI (31.1 ± 6.3 kg/m2), higher blood glucose and HbA1c level and the frequency of diabetic polyneuropathy. Patients with the classic phenotype had a higher frequency coronary artery disease (20.8 %) compared to other phenotypes. Patients with insulinopenic phenotype on hypoglycemic tablets and patients with hyperinsulinemic phenotype on insulin therapy did not have HbA1c less than 7 %. Conclusions. To personalize therapy, the phenotypic variant of type 2 diabetes should be considered, with a study of the level of C-peptide, insulin and the calculation of the HOMA-IR insulin resistance index to determine the phenotype.
Key words
References. Standards of specialized diabetes care. 9th Edition (revised). Eds. I.I. Dedov, M.V. Shestakova, A.Yu. Mayorov. Sakharnyy diabet = Diabetes mellitus. 2019; 22 (S1). [In Russian]. doi: 10.14341/DM221S1
- Genetic passport - the basis of individual and predictive medicine. Ed. V.S. Baranov. Saint-Petersburg: Izdatel'stvo N-L, 2009. 528 p. [In Russian].
- Dedov I.I., Shestakova M.V., Vikulova O.K., Zheleznyakova A.V., Isakov M.A. Diabetes mellitus in Russian Federation: prevalence, morbidity, mortality, parameters of glycaemic control and structure of glucose lowering therapy according to the Federal Diabetes Register, status 2017. Sakharnyy diabet = Diabetes mellitus. 2018; 21 (3): 144-159. [In Russian]. doi:10.14341/DM9686
- Partshaladze V.I., Goncharova O.A., Ilina I.M. Diabetes mellitus with clinical phenotype of type 2 patients with normal body weight. Svit meditsini ta biologii = World of Medicine and Biology. 2014; (3): 80-83. [In Russian].
- Ahlqvist E., Storm P., Karajamaki A., Martinell M., Dorkhan M., Carlsson A., Vikman P., Prasad R.B., Aly D.M., Almgren P., Wessman Y., Shaat N., Spegel P., Mulder H., Lindholm E., Melander O., Hansson O., Malmqvist U., Lernmark A., Lahti K., Forsen T., Tuomi T., Rosengren A.H., Groop L. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 2018; 6 (5): 361-369. doi: 10.1016/S2213-8587(18)30051-2.
- American Diabetes Association. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes – 2018. Diabetes Care. 2018. 41 (Suppl. 1): S73–S85. doi: 10.2337/ dc18-S008
- Beck-Nielsen H. Phenotypes in type 2 diabetes based on a national survey. 49th EASD Barcelona, Spain, September 23–27, 2013. Barcelona, 2013.
- Del Prato S. Treatment of type 2 diabetes based on pathophysiological knowledge. 49th EASD Barcelona, Spain, September 23–27, 2013. Barcelona, 2013.
- Donnan P.T. Derivation and validation of a prediction score for major coronary heart disease events in a U.K. type 2 diabetic population. Diabetes Care. 2006; 29 (6): 1231–1236. doi: 10.2337/dc05-1911
- International Diabetes Federation. IDF Diabetes Atlas. 8th ed. Brussels: IDF, 2017.
- Li L., Cheng W.Y., Glicksberg B.S., Gottesman O., Tamler R., Chen R., Bottinger E.P., Dudley J.T. Identification of type 2 diabetes subgroups through topological analysis of patient similarity. Sci. Transl. Med. 2015; 7 (311): 311ra174. doi: 10.1126/scitranslmed.aaa9364
- Mahajan A., Wessel J., Willems S.M., Zhao W., Robertson N.R., Chu A.Y., Gan W., Kitajima H., Taliun D., Rayner N.W. et al. Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes. Nat. Genet. 2018; 50 (4): 559–571. doi: 10.1038/s41588-018-0084-1doi: 10.1038/s41588-018-0084-1
- Simmons R.K., Coleman R.L., Price H.C., Holman R.R., Khaw K.T., Wareham N.J., Griffin S.J. Performance of the UK prospective diabetes study risk engine and the framingham risk equations in estimating cardiovascular disease in the EPIC-Norfolk cohort. Diabetes Care. 2009; 32 (4): 708-713. doi: 10.2337/dc08-1918
- Udler M.S., Kim J., von Grotthuss M., Bonas-Guarch S., Cole J.B., Chiou J., Boehnke M., Laakso M., Atzmon G., Glaser B., Mercader J.M., Gaulton K., Flannick J., Getz G., Florez J.C. Type 2 diabetes genetic loci informed by multi-trait associations point to disease mechanisms and subtypes: A soft clustering analysis. PLoS Med. 2018; 15 (9): e1002654. doi: 10.1371/journal.pmed.100265
- Yaghootkar H., Scott R.A., White C.C., Zhang W., Speliotes E., Munroe P.B., Ehret G.B., Bis J.C., Fox C.S., Walker M., Borecki I.B., Knowles J.W., Yerges-Armstrong L., Ohlsson C., Perry J.R., Chambers J.C., Kooner J.S., Franceschini N., Langenberg C., Hivert M.F., Dastani Z., Richards J.B., Semple R.K., Frayling T.M. Genetic evidence for a normal-weight "metabolically obese" phenotype linking insulin resistance, hypertension, coronary artery disease, and type 2 diabetes. Diabetes. 2014; 63 (12): 4369–4377. doi: 10.2337/db14-0318
About Authors (Correspondence):
Objective of the study was to investigate clinical features of phenotypic variants of type 2 diabetes mellitus (T2DM) for personalization of hypoglycemic therapy. Material and methods. 2085 patients with T2DM (637 men and 1148 women), mean age 58.7 ± 6.9 years, duration of diabetes 7.8 ± 6.5 years; level of glycated hemoglobin (HbA1c), creatinine, urea, total cholesterol, triglycerides, low (LDL) and high density lipoprotein, uric acid, ALT, AST, insulin, C-peptide, microalbuminuria were examined. Depending on the level of C-peptide and the index of HOMA-IR, patients were divided into 3 groups: group of insulinopenic phenotype (n = 250, 12 %), group of classical phenotype (n = 1605, 77 %) and group of hyperinsulinemic phenotype (n = 230, 11 %). Results. Patients with hyperinsulinemic phenotype differed from patients with classical and insulinopenic phenotype by later age of onset of diabetes (52.3 ± 8.1 years), high body mass index (BMI; 37.2 ± 7.4 kg/m2), blood LDL (3.38 ± 1.08 mmol/l) and creatinine level and frequency of chronic kidney disease (39.1 %). Patients with the insulinopenic phenotype had less diabetes duration (48.3 ± 7.9 years), a lower BMI (31.1 ± 6.3 kg/m2), higher blood glucose and HbA1c level and the frequency of diabetic polyneuropathy. Patients with the classic phenotype had a higher frequency coronary artery disease (20.8 %) compared to other phenotypes. Patients with insulinopenic phenotype on hypoglycemic tablets and patients with hyperinsulinemic phenotype on insulin therapy did not have HbA1c less than 7 %. Conclusions. To personalize therapy, the phenotypic variant of type 2 diabetes should be considered, with a study of the level of C-peptide, insulin and the calculation of the HOMA-IR insulin resistance index to determine the phenotype.
Full Text
Received: 03/03/2020
Accepted: 03/03/2020
