In this context, "basal" is the same as "fasting". Normal basal/fasting BG is ~75mg/dL. Diabetic (by clinical definition) is 126mg/dL or more.
Hence, significantly above 75mg/dL is "degraded". The diabetes research community is pushing to have the ADA lower threshold for "pre-diabetes" (based upon IFG -- so-called "impaired fasting glucose") reduced from the present 100mg/dL to 90mg/dL, because it is well understood at this point that anyone who has a true FBG of 90 or more is well along in the progression of diabetes and should be made aware of it.
Basal glucose metabolism is, in my opinion, significantly distinct from post-prandial metabolism. Ralph DeFronzo and his group have found that the primary defect (i.e. cause) in fasting hyperglycemia is in the skeletal-muscle non-insulin-dependent pathway (which is responsible for ~85% of glucose uptake under fasting conditions). An aging of the tissues, involving gene expression, gradually reduces the glucose uptake at normal fasting concentrations -- this results in a higher fasting level in homeostasis (or equilibrium). On the other hand, post-prandial response is highly dependent upon the insulin-dependent pathways in various tissues.
However, as loss of pancreatic function (i.e. insulin-secretory capability) always occurs in true diabetic progression, in an isolated-IFG (i.e. I have no whole-body insulin resistance or IGT -- so-called "impaired glucose tolerance" -- which is the other category of pre-diabetes) case such as myself there is an effect upon post-prandial response. For me, it is primarily a loss of acute or 1st-phase insulin response, resulting in a higher BG in the first hour or so after a meal (until the 2nd-phase insulin response kicks in). According to DeFronzo I have lost about 60% of my overall post-prandial insulin capability. This is probably due to a combination of loss of beta-cell mass/volume (including the vesicles that are used to store insulin for the 1st-phase response) and an apparent effect of elevated FBG in reducing the sensitivity of beta cells to BG concentration. Hence, there is probably both a permanent and a recoverable component to the "degradation" of pancreas function. Recovery of some of my insulin secretion would occur if I could lower my fasting BG.
Thanks for the tips, Dr. Dansinger. I think I am OK regarding particle size -- my last HDL-c = 87mg/dL and triglycerides = 55mg/dL. I haven't had NMR-measured subfractions, but with a Tg/HDL ratio < 1 I am confident that there is no degradation of particle size as in metabolic syndrome and T2DM.
I take ~2g EPA/DHA and 5000IU vitamin-D3 daily too.
Overweight, IGT and T2DM all come with elevated plasma FFA caused by IR in the adipocytes (and associated lipids degradation), but IIFG does not. Possibly the degradation of basal glucose regulation I have has resulted from metabolic syndrome that I have previously had.
If that's the case then I may be able to arrest the degradation by sticking with my current diet and exercise program. Maybe the basal regulation will eventually even improve, but if so I am guessing that will take years to become noticeable.
Thanks again for your last response. I haven't checked back in for a while and just now have read it.
I think you understand my conundrum -- what is best for me to do now that I recognize my hyperglycemia?
You might be interested in the fasting-insulin/glucose readings that I had done recently, at your suggestion. They were: FI: 2 mclU/ml, FG: 79 mg/dL
My normal FG is ~100 mg/dL -- I know that this reading was abnormally low, apparently because of some exercise (shoveling snow) done the evening prior. My HbA1c reading done at the same time was 5.6%. Recent OGTT readings were: 0-hr. 99 mg/dL, 2-hr. 91 mg/dL
My crude interpretation of all this is that my insulin sensitivity is probably even higher than normal, and that my primary problem (at this point, anyway) is loss of insulin secretion. A paper by DeFronzo et al ( http://www.ncbi.nlm.nih.gov/pubmed/18492770 ) indicates that for IIFG with FG in the 95-100 mg/dL range there is ~60% loss of pancreatic function (i.e. IS). So that's where I am at, I guess.
I wonder how I might arrest and even reverse the loss of beta-cell function, and if my own pathogenesis is purely genetic (i.e. aging of the tissues via changing genetic expression) at this point, or not.
The results of the various studies of TZD treatment of pre-diabetes are intriguing. If DeFronzo's theory of the primary defect in IIFG is correct then TZDs would seem to be my only hope of actual reversal (i.e. lowering of FG), within the scope of current knowledge. Outside of a research study, however, I recognize that few if any clinicians would choose to prescribe a TZD at my present level of hyperglycemia. I don't particularly like the idea of taking a drug, but if the progression is insensitive to anything else it might be worth considering.
I guess I probably have many years of time before progressing to diabetes, in the worst case, and hopefully the research will generate more understanding of the etiology and treatment of fasting hyperglycemia.View Thread
Thanks very much for the additional reference, Dr. Dansinger. Thanks also for your feedback. I am still struggling to develop a better understanding of my own condition and how I might better achieve predictable and measurable results by optimizing diet and exercise.
The paper that I cited reflects more recent research than that of the more general diabetes treatise that you cited in your reply, I think. In addition, its study focuses on fasting (or postabsorptive) homeostasis only, in the range between normal and diabetic BG concentrations. I am particularly interested in this because I think it distinguishes my own condition, although I certainly recognize that there is an associated degradation in glucose-stimulated insulin secretion (or postprandial response) in my own case and in IFG in general.
Most importantly, the more recent DeFronzo study seems to point more to a change in the "law-of-mass-action" (i.e. non-insulin-dependent) response of skeletal-muscle (glucose uptake) to basal BG concentration, rather than that to the basal plasma-insulin concentration, as the primary effect in the pathogenesis of IFG leading to diabetes.
Hence, while the earlier-research summary indicates IR (e.g. GLUT4) may be at work even in lean individuals, the later study seems to point to a BG-dependent (and insulin-independent, e.g. GLUT1) mechanism. I speculate that this mechanism may be much more persistent than that of insulin resistance (which I have admittedly had in past).View Thread
You may recall our conversation from a few weeks ago. I have isolated IFG (borderline at ~100mg/dL FBG). I am also fit (~10% body fat), although I have been in the range of BMI between 25 and 30 (overweight) for much of my adult life. I am 52 years old (male).
I have taken your suggestion and requested a fasting insulin/glucose test to assess HOMA parameters in Jan. 2011.
One topic of great interest to me (since I recently discovered my elevated HbA1c and then IFG) is the notion of hepatic insulin resistance and whether it is involved in the progression of fasting hyperglycemia in the sub-diabetic range (<126mg/dL). If so the HOMA is of more interest for my condition than if not. In fact, it might be argued that if not, then the fasting insulin measurement is of no use at all to me.
I recommend you (and others) to the following paper by DeFronzo et al, in which they discuss their study that appears to disprove the hypothesis that hepatic insulin resistance (i.e. failure to fully suppress excess gluconeogenesis by adequate endogenous insulin secretion) is involved in pre-diabetes, but rather only in frank diabetes. They also conclude that basal insulin secretion rates remain normal for fasting BG < 126mg/dL.
As the paper's title suggests, the authors conclude that the primary factor in causing nondiabetic fasting hyperglycemia is decreased glucose clearance. Furthermore, their measurements indicate that a large proportion of the decrease must be due to insulin-independent glucose uptake in the skeletal muscle (e.g. that associated with GLUT1 transport).
I would interpret the paper's implications for my own condition to be that my primary defect remains in the skeletal muscle (probably exclusively), and involves gene expression that must be reverted back to a "normal" state such as that I presumably had when much younger.
I have been using a low-carb diet for ~one year (since before I discovered by BG-regulation problem) and intense physical training since Aug. 2010. This is a relatively small period of time, but I see no significant change in my FBG yet. My HbA1c has dropped from 5.7 to 5.4 but I attribute this to the constant (but temporary) knocking down of my FBG from the high-intensity exercise.
Hence, my problem has persistence to the extent that it looks to be either irreversible or something that will require years rather than months to reverse.
I have read about anecdotal cases of people who normalized very high BG concentrations in small periods of time such as a few months or even weeks (using diet changes). I suspect that this is only possible for those with very high whole-body insulin resistance and possibly only those with genetic immunity to diabetes (and hence, larger-than-normal compensatory pancreatic beta-cell mass). But I suspect that IFG is intrinsically a very slowly evolving derangement.
I would be interested in any comments you have about the paper and my own interpretations of it. Hopefully this subject will be of interest to others with isolated IFG who are trying to arrest and reverse the progression of this condition. My impression is that there has been little research on IFG as opposed to IGT, and that very little expertise with respect to IFG exists in the medical and research community.View Thread