This new USA study is hardly breaking news, we have known it for at least a generation :
it shows again that delayed  intense blood   Glucose Control introduced in longstanding chronic diabetic patients with sulphonylureas , glitazones or insulin has no benefit on Vascular Complications in Veterans with Type 2 Diabetes ie adverse  degenerative outcomes.

However, it is unclear why this trial did not use metformin to it’s full potential. The dose specified in Methods (Abraira 2002)  was to titrate dose to a maximum of 2gm/day, whereas the average tolerated dose is almost 3gm/day (ie some people metabolize faster and safely tolerate more)  provided the dose is slowly titrated up from no more than 125mg/day till the highest tolerated dose is found.
And the trial  further diminished  the crucial benefit of metformin by an  unfounded  assumption  that metformin works only in the obese- so in this trial  patients were excluded from metformin with BMI <27kg.
So  that BMI threshold included in the  metformin trial  only  men with body fat above about 22% or body fat > 20kg; or women above 34% or body fat > 20kg (extrapolated from eg Knapik ea 1982 in US military personnel) ; whereas it is well established that risk rises progressively from BMI above about 22.5kg or body fat much above about 15kg. Thats why  the now-recognized definition of overweight is BMI>25kg. Only top bodybuiders, superathletes will have BMI up to perhaps 27kg/sqm  with fat mass down to 5% ie lean mass index of 25.6kg/sqm (see textbooks on bodymass and fitness of Gilbert Forbes; Tony Lohman).  The average  urban non-athlete non-labourer is already carrying increasing excess (and metabolically disadvantageous) body fat the higher BMI exceeds ~23kg/sqm- with in men lean mass index  LMI   about  19kg/sqm, in  women LMI often below 17kg/sqm.

It  again bears out the devastating futility, the criminal negligence  of not reversing overweight early,  delaying metformin, fish oil, nicotinamide  and other insulin sensitizing antioxidant nitric oxide boosters  (including appropriate non-oral HRT)   till obesity let alone established hypertension, lipidemia, cardio/vascular-renal disease, cancer  or diabetes develops.

The four major  metformin diabetes prevention trials (in different continents) repeatedly discussed in this column  show how well even a modest dose of metformin – 750mg to 2000mg  a day –  can reduce incidence of  new diabetes type 2 by 30 to 90%- so metformin titrated to tolerance plus early & permanent fish oil and other insulin sensitizing antioxidant nitric oxide boosters  (including appropriate non-oral HRT) can almost abolish type 2 diabetes if started early enough and maintained.


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