How genetic traits contribute to early diabetes development and metabolic problems in South Asians

Research highlights genetic factors that promote earlier onset of diabetes, lower insulin production, and obesity patterns in South Asians.

Genetic predispositions associated with lipodystrophy and insulin deficiency in British-Pakistanis and British-Bangladeshis may result in earlier onset of type 2 diabetes (T2D) as well as faster progression of complications and response to drug therapy. It is also associated with a decrease in insulin dependence.

recent natural medicine The study investigated why South Asians are more vulnerable to early onset and progression of type 2 diabetes.

Prevalence of T2D in South Asians

Compared to Europeans, South Asians are diagnosed with T2D at a younger age and also have a lower BMI. For example, Asian Indians are four times more likely to develop diabetes before age 40 than Europeans. A recent study revealed that 12.7% of South Asians develop T2D.

A previous study conducted in India used a phenotypic genotyping strategy and detected a high prevalence of severe insulin deficiency diabetes (SIDD) in South Asians. Studies in people of European descent have shown the prevalence of insulin resistance. However, there are not many genetic studies aimed at understanding the genetic basis of early T2D onset and progression in South Asian populations.

Compared with polygenic risk score (PRS), partitioned polygenic score (pPS) was found to be more efficient in identifying associations with diabetes-related complications.

Multiple studies have shown that the genetic makeup and clinical phenotype of T2D differ between South Asians and Europeans. It is important to understand whether pPS strategies can elucidate the genetic basis of this difference.

About research

In the current study, a pPS strategy was used to understand the etiology behind the early onset of T2D in Pakistani-British and Bangladeshi-British people. All relevant data were collected from Genes & Health. This longitudinal community-based study included British Bangladeshis and British Pakistanis aged 16 and over living in the UK.

At baseline, all recruited participants provided saliva samples for genotyping and completed a short questionnaire regarding demographic information. Both primary and secondary care data were obtained from the UK NHS electronic health record (EHR).

The pPS of 12 diabetes-related genetically determined endotypes was determined using PLINK. These include three endotypes related to insulin secretion (beta cell 2), glucose sensing (beta cell 1), and insulin production (proinsulin). Three clusters associated with insulin resistance and abnormal fat accumulation. and six clusters were associated with insulin resistance and deficiency effects.

Research results

The current study included 9,771 British Bangladeshis and British Pakistanis diagnosed with T2D and 34,073 people without diabetes (controls). Bangladeshis were found to be diagnosed with T2D at a younger age and have a lower body mass index than Pakistanis. Bangladeshi women also gestational diabetes (GDM) than Pakistani women.

Five years after being diagnosed with T2D, Pakistanis had higher glycated hemoglobin (HbA1c) and BMI than Bangladeshis. It was observed that Pakistanis were more likely to receive insulin prescriptions and develop nephropathy than Bangladeshis.

In the current study, we observed that Bangladeshis had higher unmodified pPS than Pakistanis, especially beta cell 2, obesity, and lipodystrophy 1. The distribution of pPS was compared between individuals of European and South Asian ancestry diagnosed with T2D, showing that South Asians had higher scores for some pPS, particularly beta cell 2 and lipodystrophy 1. It was done. However, obese pPS was found to be higher in individuals who: European ancestors.

Compared with the control group, the scores of all pPS except bilirubin were higher among GDM cases, T2D cases, and T2D onset after GDM. After adjusting for gender and ancestry, an association between pPS and T2D risk was observed. This association also existed between pPS and GDM and T2D after GDM. In both cases, the strongest association was observed between beta cell 1 and beta cell 2.

All pPS (except bilirubin) were associated with earlier age of T2D onset. However, the strongest associations were with beta cells 2, obesity, and lipodystrophy 1. In the present study, an association between pPS and response to oral antidiabetic drugs was established through HbA1c measurements.

For example, higher beta cell 2 pPS scores were associated with higher HbA1c after initiation of thiazolidinediones. Interestingly, beta cell 2 and lipodystrophy 1 pPS were associated with progression on insulin treatment. Previous studies have highlighted that rapid progression to insulin therapy indicates poor T2D management.

conclusion

In the current study, we observed that beta cell 2 and lipodystrophy 1 were strongly associated with T2D and GDM, and younger than those diagnosed with T2D. The study concludes that South Asians, who have a higher genetic risk for insulin deficiency (beta cell 2) and lipodystrophy, are at increased risk for T2D, insulin dependence, and poor response to drug therapy.