Increased weight and Insulin resistance lead to improved glycemic control

Somebody needs to explain this to me. This, once again, deals with Ketosis Prone Type 2 Diabetes but I don't care. This seems to go against everything that I know about being T2. This is from two of the seminal papers on Ketosis Prone Type 2 Diabetes so it isn't junk science. I went back and read these papers because I was researching what was meant by "near-normoglycemic remission".  This data caught my eye and when I looked at other papers, I found confirmation.


Ketosis Prone T2 Diabetics are known for the fact that they can suddenly go into acute insulin failure and essentially become T1's, some will even stay T1's, with no autoimmune factors. The others will recover their beta functioning incredibly fast, we are talking weeks, if given insulin therapy. Even though their IR hasn't receded on bit, they will still proceed to stabilize their blood sugars at or near normal levels. Many, can and do,  require only diet and exercise regimens. This is weird enough but this next part is inexplicable to me.


Weight does not really play a part in KPD. There are just as many thin KPD's as obese ones.They both are prone to DKA just as much. The recovery, however, is something different. The KPD's who recover fastest and have the lowest A1c's tend to be the ones who put on weight. Weight gain is the best predictor of  near-normoglycemic remission. If we follow the logic, these are people who gain glycemic control by increasing their insulin resistance. How? This makes no sense. The thin ones don't do as well as those who put on weight. It gets better. Those with metabolic syndrome actually do better than those without metabolic syndrome. I can not wrap my head around this. Here are some of the quotes from these papers


We also noted significant weight gain associated with improvement of glycemic control, regardless of what therapy was used. Insulin-treated patients gained more weight than individuals on other therapies.

Our study also indicates that weight-gain is a good clinical marker of improved glycemic control, regardless of what therapy is used.

There was a significant correlation between changes in HbA1c and weight changes (r 5 0.45, P , 0.001, n 5 54) in both treatment groups. Patients with greater improvement in HbA1c had greater weight gain. Weight gain after initiation of diabetes treatment was 6.6 6 12.5 kg, regardless of what therapy was used. However, 17 patients continued to lose weight during the years of follow-up. These patients had a follow-up HbA1c of 11.4 6 3.5%. Of the patients that lost weight during the study, 5 were on insulin and 12 were on diet and/or oral agent therapy (7 on diet therapy alone, 2 on glyburide/metformin, 2 on glyburide alone, and 1 on glyburide/troglitazone combination). In the 37 patients who gained weight, HbA1c was 8.0 6 2.5% at follow-up. Of the patients that gained weight, 28 were on insulin and 9 were on oral agents or diet. The patients in the insulin-therapy group that gained weight had a significantly lower HbA1c than the patients in the diet and/or oral agent group that gained weight (P 5 0.01; difference of 2.6%, 95% CI 0.83– 4.4%). There was also a significant difference of 3.4% in HbA1c in patients that gained weight (regardless of therapy) compared with those that lost weight during the observational period (P , 0.0001, 1.7–5.1%). The patients on insulin therapy had a mean weight gain of 11.0 6 11.2 kg (P , 0.0001, 6.6 –18.5kg) versus non–insulin-treated patients.

Other than weight gain, there was no difference in diabetes-related complications between treatment groups in this short study period.

Idiopathic Type 1 Diabetes in Dallas, Texas A 5-year experience

Antonio Piñero-Piloña, MD, 

Patrick Litonjua, MD, 

Larissa Aviles-Santa, MD and  

Philip Raskin MD

DIABETES CARE, VOLUME 24, NUMBER 6, JUNE 2001

In conclusion, over 40% of patients in a multi-ethnic cohort of indigent patients with ketosis-prone diabetes have the MetS. These patients have better glycemic control, higher h-cell functional reserve, and a greater likelihood of following a noninsulin-dependent course, than do those who do not have the MetS.




The glycemic control at baseline was very poor in both groups’ mean Hba1c of 13%; it significantly improved in both groups, but it was significantly better in the +MetS group. Improved glycemic control has been well described in ketosis-prone Type 2 diabetes mellitus 
(Balasubramanyam et al., 1999; Banerji et al., 1994; Maldonado et al., 2003; Umpierrez et al., 1999).
Preserved h-cell function is a feature of ketosis-prone Type 2 diabetes (Balasubramanyam et al., 1999; Banerji et al., 1994; Maldonado et al., 2003; Umpierrez et al., 1999). In both groups, the h-cell function was lower on presentation and improved significantly in both groups at 6 and 12 months of follow-up. Based on the C-peptide, C-peptide-to-glucose ratio, and C-peptide response to glucagon stimulation, the +MetS group had significantly higher h-cell functional reserve both at presentation and during follow-up. Autoantibodies against the h-cell were more frequently present in the MetS group.



Presence of the metabolic syndrome distinguishes patients with ketosis-prone diabetes who have a Type 2 diabetic phenotype
Max E. Otinianoa, Ashok Balasubramanyama,b, Mario Maldonadoa,b,
Journal of Diabetes and Its Complications 19 (2005) 313– 318


Don't think that this is some weird or isolated diabetes, a conservative estimate puts the number to be, at least, 1 million diabetics in this country alone, twice as high would be more realistic. Still this doesn't make much sense.

Mike

It took me a couple of months but here is my answer to this post.