Metabolic health: insulin resistance, visceral fat, CGMs, and where the GLP-1 class fits

What insulin resistance is

Insulin is the hormone that tells muscle, liver and fat to take up glucose and stop releasing fuel. Insulin resistance is the state in which those tissues need more and more of it to respond, so the pancreas makes more. Glucose stays normal for years — a decade or more — because the extra insulin is holding it down. That is why a "normal" fasting glucose is so often false reassurance: the first marker to move is fasting insulin, and most people have never had it measured.

The downstream list is long. High insulin blocks fat release, drives triglycerides and small dense LDL, raises blood pressure through sodium retention, and is associated with higher rates of colorectal, breast and pancreatic cancer and with Alzheimer's disease, which some researchers now call type 3 diabetes. In the Interheart study, abdominal obesity and diabetes together accounted for about a third of the population risk of a first heart attack.

Visceral fat: the fat that matters

Fat under the skin is mostly harmless storage. Fat around the organs — visceral fat, and the fat inside the liver and pancreas — is metabolically active: it drains straight into the liver, secretes inflammatory cytokines and is the strongest anatomical predictor of insulin resistance. Two people with the same BMI can have a three-fold difference in visceral fat, which is why BMI is a poor guide and waist is a better one.

Reading your own numbers

HOMA-IR is fasting glucose (mmol/L) multiplied by fasting insulin (µIU/mL), divided by 22.5. Under 1.0 is insulin-sensitive; 1.0–2.0 is the band most middle-aged adults sit in; above 2.5 is clear resistance. An HbA1c above 36 mmol/mol (5.4%) with a fasting insulin above 8 is the picture of early resistance in someone whose glucose still looks fine.

A continuous glucose monitor worn for two weeks is the most instructive thing most people can do for their metabolic health, and also the most over-interpreted. What it is good for: seeing which meals produce a spike above about 8 mmol/L (140 mg/dL), how long the return takes, what a walk after eating does (a lot), what a bad night does (a lot), and whether the dawn rise is large. What it is not: a diagnostic tool, or a reason to fear a banana. Healthy people spike, and the evidence that flattening every spike improves outcomes in non-diabetics does not exist yet. Use it to learn for a fortnight, twice a year, not to live by.

The GLP-1 class: what the trials showed

The incretin medicines have changed what is possible in fat loss, and the numbers are worth knowing precisely because the marketing around them is loose.

Three honest caveats. First, in the STEP 1 DEXA sub-study, about 40% of the weight lost was lean mass, which in a sedentary adult over fifty is muscle they cannot afford. Second, in the extension studies two-thirds of the weight returned within a year of stopping, because the appetite that was suppressed comes back and the habits were never built. Third, these are prescription medicines — the trial results apply to the trial doses under medical supervision, and anything labelled "research" is outside that.

Keeping the muscle

Whether the deficit comes from a medicine, a diet or both, the rules for protecting lean mass are the same and the evidence is consistent:

• Protein at 2.0–2.2 g/kg of target body weight, split over three or four meals. Appetite suppression makes this hard and is the main reason people lose muscle on the GLP-1 class.
• Resistance training twice a week, non-negotiable. In trials of weight loss with and without lifting, the lifters kept most of their lean mass; the dieters alone lost a quarter or more.
• A rate of loss under 1% of body weight a week. Faster than that and the proportion lost as muscle climbs.
• A DEXA before and every 12 weeks. The scale cannot tell you what you lost.
• Creatine, 3–5 g a day, which has evidence for preserving lean mass in a deficit.

What to measure

• Fasting insulin and glucose (HOMA-IR) and HbA1c at baseline and every 3 months while losing fat.
• Waist-to-height ratio monthly; DEXA visceral fat and lean mass every 12 weeks.
• ApoB and triglycerides, which usually fall with visceral fat and confirm the loss is the right kind.
• Liver enzymes and a liver-fat estimate if ALT is raised or the waist is over 100 cm.
• A two-week CGM at baseline and once the weight has moved, to see what changed.
• Grip strength every 12 weeks: if it is falling while the weight falls, the protocol is wrong.

Where peptides and therapies fit

The research library has pages on the two compounds people ask about most — tirzepatide and retatrutide — describing what each is studied for, the labs, the week-by-week picture and the mistakes. The GLP-1 transition guide is for anyone already on a prescribed incretin who wants to understand how a protocol phases rather than stacks. And the fat-loss goal page is where all of it sits together with the protein, the lifting and the DEXA calendar that stop the muscle going with the fat. For visceral fat specifically, tesamorelin is the one compound with randomised data, and the hormones article explains why testosterone and insulin resistance are so often the same conversation in men over fifty.

Common mistakes

• Trusting a normal fasting glucose. Insulin moves first, by years.
• Weighing instead of measuring. Waist and DEXA; the scale cannot see visceral fat or muscle.
• Living by the CGM. Fearing fruit while sleeping five hours is a precise way to miss the point.
• A GLP-1 medicine without protein and lifting. Forty per cent of the loss is lean mass if nothing is done about it.
• Stopping the medicine the day the goal is reached. The appetite returns; the habits have to be in place first, and the exit is phased.
• Treating cardio as the fat-loss tool and lifting as optional. It is the other way round in a deficit.