D2I2.
metabolic⚑ High burden in India

Type 2 diabetes

Type 2 (T2D), formerly known as adult-onset diabetes, is a form of diabetes that is characterized by high blood sugar, resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, and unexplained weight loss. Other symptoms include increased hunger, having a sensation of pins and needles, and sores (wounds) that heal slowly. Symptoms often develop slowly. Long-term from high blood sugar include heart disease; ; diabetic retinopathy, which can result in blindness; kidney failure; and poor blood flow in the lower limbs, which may lead to amputations. A sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.

Underlined words are explained — tap any of them.

How common · Diabetes prevalence, adults 20–79 (%)
10.5% (2024)
India
10.8% (2024)
World
Source: Our World in Data / IHME GBD

Symptoms — what it feels like

  • ·Increased thirst, frequent urination, unexplained weight loss, increased hunger

Causes — why it happens

  • ·, lack of exercise,

How it's found

  • ·Blood test

Prevention

  • ·Maintaining normal weight, exercising, healthy diet

Treatment

  • ·Dietary changes, exercise, medication such as metformin and , bariatric

Complications

  • ·Hyperosmolar hyperglycemic state, diabetic ketoacidosis, heart disease, , diabetic retinopathy, kidney failure, lower-limb amputations

Outlook

  • ·10 year shorter life expectancy
An open question — could you help answer it?

A European-trained for type 2 flags 30.6% of Telugu (India) people as high-risk - vs the 10% it was designed for. That's a 3.1x mis-stratification: the score's 'average' is set to European , so it systematically mis-reads South Asians (a +0.80 SD mean shift).

A study that would help: Recalibrate PGS000033 on an Indian (define the threshold on South-Asian, not European, risk) and quantify how many people get correctly re-classified. A concrete, fundable validation study once a genotyped+phenotyped Indian sample is in hand.

Genomics deep dive · verified

The risk score that cries wolf for Indians — over the largest diabetes population on Earth

The finding

A European-trained (PGS000033) flags 30.6% of Telugu Indians as high-risk, against the 10% it was calibrated to — a 3.1x mis-stratification (our analysis on South Asian samples). The score's baseline is European; applied to Indian DNA it reads risk off a mis-set ruler.

Why India specifically

India has over 100 million adults with (ICMR-INDIAB national study, 2023), and South Asians develop it younger, at lower BMI, with more central fat — the 'thin-fat' . A tool that systematically mis-ranks them isn't academic: it mis-triages the largest diabetes population on Earth.

What's known — and the gap

The -frequency mean-shift that drives the mis- is real and measurable. What's missing is a South-Asian-calibrated score validated against Indian outcomes — the training cohorts barely include Indians. Effect sizes and linkage patterns may differ too, which frequency math alone can't capture.

A study you could fund

Recalibrate PGS000033 on an Indian genotyped + phenotyped (even a few thousand people), set the high-risk threshold on South-Asian rather than European risk, and measure how many people get correctly reclassified. A clean, publishable validation once a sample is in hand.

Sources
  • Martin et al., 'Clinical use of current polygenic risk scores may exacerbate health disparities', Nature Genetics 2019
  • Anjana et al. (ICMR-INDIAB), Lancet Diabetes & Endocrinology 2023 — ~101M Indians with diabetes
  • D2I2 PRS-transferability analysis (1000 Genomes phase 3)
Plain-language summary adapted from Wikipedia. Not medical advice.