Increased weight and insulin resistance revisited

This relates to a baffling previous post.Here This was puzzling because it involved KPD diabetics gaining weight after a DKA event and becoming normoglycemic. I've discussed remission in KPD's before and though the mechanism isn't well understood, it is known to be common enough to be considered a part of the KPD syndrome. No, what upset the apple cart here was that thin KPD's did not do as well as the ones who gained weight. This seems counter to all the advice about weight loss that is given to diabetics. Almost the first thing a doctor will say to a patient is to lose weight. If a KPD followed this advice their blood sugars would rise and lowering blood sugars is central tenet of all things diabetic. What the heck is going on here?

I am now going to put forth an idea that popped into my head after reading a post by Ned Kock over at Health Correlator. Here What got my attention were people who were heavy but were more insulin sensitive then their control group. What was even better: once they received medication they began to lose weight but became more insulin resistant with a rise in blood sugar.

Insulin Resistance is very much at the heart of obesity and thinness as far as I can see but it is also one of the central aspects of Ketosis Prone Type 2 diabetes. Pal Jabekk speaks of the fact that insulin resistance is a body wide behavior. I agree given insulin's importance in energy metabolism obviously everything has critical involvement with it. This doesn't, however, mean that insulin is used at the same rate through out the body all the time. At any given moment, there will always be some systems that are more or less resistant.

This brings me back to the puzzle of KPD weight gain while at the same time reaching near normal blood sugars. First of all KPD's are infamous in the fact that weight is not an issue. Just as many KPD's are thin as obese. Some have separated this along the lines of those who lack sufficient insulin so that they become thin and those who have plenty so they become fat.

When the DKA or severe ketosis event occurs KPD's, who recover, are shown to have a low normal reading of C-peptides. The cut off that has been cited is .9. In six months, it is common for this to go back into the normal range and higher. It is also known that KPD's recover near normal blood sugars even though their measurable IR isn't reduced one jot. It should be noted, as well, that the best blood sugars tend to go to the heavier KPD's and not the thin ones.

Given that the IR is still high, the  C-pep is normal or above and the blood sugars have normalized, we have to assume that there is relatively enough insulin present. What is the difference between thin and obese?

Now the leap of faith. It has to be relative insulin sensitivity issues. We can see with a thin person that insulin is putting relatively more energy in other systems besides fat. What those systems are we really don't know. What we can tell, however, is those systems on the whole are more sensitive to insulin than fat. Likewise, if the person is putting on weight then their adipose is relatively more sensitive to insulin than other body systems.

Now my thinking about the KPD's gaining weight with better A1c's. I believe fat works better for glucose storage then muscle or other systems. You can look at obesity as the body's way to reacting to high amounts of glucose. This is why I believe there are so many heavy people. Obviously, the body is sending glucose everywhere but the fat cells seem to get more. If we make this about controlling blood sugar then the fat cells become like the catch basin for the extra glucose in the system.

A thin KPD is relatively more insulin resistant in the fat cells, and this is why I say fat works better, sending glucose to other systems with fat lower down on the list doesn't normalize blood sugars as well as those who can send it to fat. So thin KPD's are typically not going to have blood sugars as good as heavier KPD's. This would also say that thin KPD's are more at risk of relapse to DKA then heavier KPD's. I would also add that this probably isn't how normal people work but we have broken metabolisms. Our livers are pretty much blind to insulin.

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.