• Maryam Wahid Foundation University Medical College Islamabad Campus
  • Mohammad Kamran Allama Iqbal Medical College, Lahore. Pakistan


Background: Mitochondrial DNA mutation and hormonal imbalance is involved in the pathogenesis of early onset diabetes but data is lacking in Pakistani population. The study was planned to delineate the clinical presentation of early onset diabetes with possible hormonal and genetic etiological factors and aascertain the possible etiological role of insulin and glucagon in these patients either on oral hypoglycaemic or subcutaneous insulin therapy. Methods: Retrospective, analytical case control study with conventional sampling technique carried at Centre for Research in Experimental and Applied Medicine (CREAM) affiliated with the department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi from Dec 2006 to July 2011. Study included the patients (20–35 years of age) with early onset diabetes on oral hypoglycemic (n=240), insulin therapy (n=280), and compared with non-diabetic healthy controls (n=150). A fragment surrounding tRNALeu (UUR) gene was amplified by AmpliTaq from mtDNA which was extracted from peripheral blood leucocytes. Then it was subjected to restriction endonucleases, ApaI for A3242G mutation and HaeIII for G3316A mutation detection. Plasma glucose, glycosylated Hb, osmolality, insulin and glucagon levels along with ABGs analysis was also done. Results: Non diabetic controls comprised of 51% males and 49% females, diabetics on oral hypoglycemic 60% males and 40 % females and on insulin therapy 54% males and 46% females. Insulin dependent diabetics had statistically significant hyperglucagonemia, acidemia and bicarbonate deficit. MtDNA A3242G and G3316A mutations were not detected. Conclusion: relative hyperglucagonemia and acidemia in Insulin dependent diabetics was a potent threat leading to DKA. The absence of two mtDNA mutations in ND1 gene rules out the possibility of involvement of these mutations in early onset diabetes in Pakistani population. Keywords: MtDNA; Mt-ND1 gene; NADH dehydrogenase; Hyperglucagonemia 

Author Biographies

Maryam Wahid, Foundation University Medical College Islamabad Campus

Professor and HODDept of Biochemistry

Mohammad Kamran, Allama Iqbal Medical College, Lahore. Pakistan

associate professordept of Surgery


Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of Diabetes estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27(5):1047–53.

Devendra D, Liu E, Eisenbarth GS. Type 2 diabetes: recent developments. BMJ 2004;328(7442):750–4.

Bhatia S, Rachna, Bansal P, Mani S. Mitochondrial diabetes: Differential diagnosis, features, and its possible management. JISMA 2014;27(4):213–5.

Walker JN, Ramracheya R, Zhang Q, Johnson PR, Braun M, Rorsman P. Regulation of glucagon secretion by glucose: paracrine, intrinsic or both? Diabetes Obes Metab 2011;13(Suppl 1):95–105.

Lehto M, Wipemo C, Ivarsson SA, Lindgren C, Lipsanen-Nyman M, Weng J, et al. High frequency of mutations in MODY and mitochondrial genes in Scandinavian patients with familial early onset diabetes. Diabetologia 1999;42(9):1131–7.

Pearson ER, Badman MK, Lockwood CR, Clark PM, Ellard S, Bingham C, et al. Contrasting diabetes phenotypes associated with hepatocyte nuclear factor – 1alpha and – 1beta mutations. Diabetes Care 2004;27(5):1102–7.

Starkov AA. The role of mitochondria in reactive oxygen species metabolism and signaling. Ann. N Y Acad Sci 2008;1147:37–52.

Tuppen HA, Blackely EL, Turnbull DM, Taylor RW. Mitochondrial DNA mutations and human disease. Biochim Biophys Acta 2010;1797(2):113–28.

Patti ME, Corvera S. The role of mitochondria in the pathogenesis of type 2 diabetes. Endocr Rev 2010;31(3):364–95.

Dongre UJ, Meshram VG. Is mitochondrial DNA responsible for maternally inherited type 2 diabetes mellitus? A hypothetical review. Int J Pharm Sci Rev 2014;28(1):179–87.

Su SL, Kou CL, Liu CH. Diabetes and mitochondria. Chang J Med 2013;11(1):1–7.

Iwasawa R, Mahul Mellier AL, Datler C, Pazarentzos E, Grimm S. Fis1 and Bap31 bridge the mitochondria – ER interface to establish a platform for apoptosis induction. EMBO J 2011;30(3):556–68.

Chen YN, Liou CW, Huang CC, Lin TK, Wei YH. Maternally inherited diabetes and deafness (MIDD) syndrome: A clinical and molecular genetic study of Taiwanese family. Chang Gung Med J 2004;27(1):66–72.

Rosenthal EL, Kilney PR, Boerst A, Telian SA. Successful cochlear implantation in a patient with MELAS syndrome. Am J Otol 1999;20(2):187–91.

Assal J, Groop L. Definition, diagnosis and classification of diabetes mellitus and its complications. World Health Organ. 1999;1–65.

Ohkubo K, Yamano A, Nagashima M, Mori Y, Anzai K, Akehi Y, et al. Mitochondrial gene mutations in the tRNALeu(UUR) region and diabetes: prevalence and clinical phenotypes in Japan. Clin Chem 2001;47(9):1641–8.

Pranoto A. The association of mitochondrial DNA mutation G3316A and T3394C with diabetes mellitus. Folia Medica Indones 2005;41(1):3–8.

Morris CJOR, Morris P. Separation methods in biochemistry. London. Pitman Press 1976;2:93–148.

Achilli A, Olivieri A, Pala M, Hooshiar Kashani B, Carossa V, Perego UA, et al. Mitochondrial DNA backgrounds might modulate diabetes complications rather than T2DM as a whole. PLoS One 2011;6(6):e21029.

Wang S, Wu S, Zheng T, Yang Z, Ma X, Jia W, et al. Mitochondrial DNA mutations in diabetes mellitus patients in Chinese Han population. Gene 2013;531(2):472–5.

Yusnita Y, Norish D, Rahman AJ. Mutations in mitochondrial NADH dehydrogenase subunit 1 (mtND1) gene in colorectal carcinoma. Malays J Pathol 2010;32(2):103–110.

Bansal P, Wang Q. Insulin as a physiological modulator of glucagon secretion. Am J Physiol Endocrinol Metab 2008;295(4):751–61.

Piero MN, Nzaro GM, Njagi JM. Diabetes mellitus–a devastating metabolic disorder. Asian J Biomed Pharm Sci 2014;4(40):1–7.

Godoy-Matos AF. The role of glucagon on type 2 diabetes at a glance. Diabetol Metab Syndr 2014;6(1):91–5.

Gromada J, Franklin I, Wollheim CB. Alpha cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocr Rev 2007;28(1):84–116.