“Know whether you are prone to diabetes”
Type 2 diabetes (T2D) is a complex disease involving the interaction of genetic and lifestyle risk factors that contribute to insulin resistance and beta-cell dysfunction. We have customized a 56- gene panel covering multiple biological pathways that unravels the molecular mechanisms and etiological factors contributing to T2D, thus facilitating early risk prediction of T2D. This enables effective preventive strategies in high-risk individuals. In addition, this NGS-based method covers variants in coding and non-coding regions in the key candidate genes. This is specifically important given the high incidence of T2D in the United States and the global population.
Maturity-onset diabetes of the young (MODY) develops after 25 yrs and is heritable, contributing to 1 – 2% of diabetes cases. The inheritance is of an autosomal dominant pattern involving 11 candidate genes. Insulin therapy is required in the affected individuals except for those having GCK genetic variants.
Candidate genes: ABCC8, CEL, GCK, GLIS3, HNF1A, HNF1B, HNF4A, KCNJ11, NEUROD1, PDX1, WFS1
Glucose sensing plays a pivotal role in the temporal regulation and amplitude tuning of insulin release by the pancreatic beta cells. Insulin secretion defects are also caused by pathogenic variants in specific candidate genes.
Candidate genes: ABCC8, GCK, INS, KCNJ11
PPARgamma (PPARG) is enriched in adipose tissue and plays a significant role in insulin sensitization. Stimulating PPARG improved glucose tolerance and insulin sensitivity. PPARGC1B stimulates several transcription factors and nuclear receptors, executes fat oxidation, non-oxidative glucose metabolism, and regulates energy expenditure. This is downregulated in prediabetic and T2D patients.
Candidate genes: PPARG, PPARGC1B
Obesity and central adiposity are well-documented risk factors for insulin resistance, T2D, and cardiometabolic disorders. Certain genetic variants, as mentioned below, increase body mass index and waist circumference, thus increasing the risk of T2D.
Candidate genes: ADRB2, ADRB3, AGRP, BDNF, ENPP1, GHRL, LEP, LEPR, MC4R, NTRK2, PCSK1, PPARGC1B, SDC3, SIM1, UCP3
ABCC8, ADRB2, ADRB3, AGRP, ALMS1, ARL6, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, BDNF, CARTPT, CEL, CEP290, EIF2AK3, ENPP1, FOXP3, GCK, GHRL, GLIS3, GNAS, HNF1A, HNF1B, HNF4A, INS, KCNJ11, LEP, LEPR, MAGEL2, MC4R, MKKS, MKS1, NEUROD1, NEUROG3, NTRK2, PCSK1, PDX1, POMC, PPARG, PPARGC1B, PTF1A, PYY, RFX6, SDC3, SDCCAG8, SIM1, TRIM32, TTC8, UCP1, UCP3, WDPCP, WFS1
Pancreatic islet-cell hyperplasia
Large for gestation
Transitory neonatal diabetes mellitus
Intrauterine growth retardation
Failure to thrive
Based on the clinical manifestations or family history of diabetes, your physician will recommend undergoing the test. Pre-test and post-test genetic counseling will be provided to explain the utility and limitations of this test. This test is highly sensitive and specific in identifying heritable causes of diabetes and hence has higher clinical utility in diagnosing even asymptomatic individuals at risk of developing diabetes. This can be performed in all age groups. Given available preventive strategies, early diagnosis of heritable causes is of prime importance to reduce disease burden.
Your health care provider will collect the whole blood sample in EDTA and collect all the necessary demographic details along with clinical and family history. The sample will be transported at ambient temperature to the lab for further processing.
Genomic DNA will be extracted from the given whole blood sample. The extracted DNA will be assessed for its quality and quantity. Next-generation sequencing (NGS) will be performed to amplify and enrich the target genes to identify the pathogenic variants. American college of medical genetics (ACMG) guidelines will be followed to report variants of pathological relevance. Bioinformatics pipelines are customized to enable the detection of known and novel variants. A genetic counselor will explain to you the significance of the findings by considering the pathogenicity of identified variants, clinical history, and pedigree analysis. The results will be communicated to the treating physician to enable further intervention.