Saturday, May 25, 2019

Retrospective #99: “Natural History of Type 2 Diabetes”

“Natural History of Type 2 Diabetes” is a heading in a paper by Ralph A. DeFronzo, MD. Dr. DeFronzo is using the medical phrase “natural history” to describe the progression of a disease from incidence to diagnosis.
The paper was published in the American Diabetes Association’s magazine, Diabetes, after he presented the Banting award lecture at the ADA’s 2008 annual meeting in San Francisco. This paper caught my attention for a statement Dr. DeFronzo made about Pre-diabetes: “In summary, individuals with IGT [impaired glucose tolerance] are maximally or near-maximally insulin resistant, they have lost 80% of their β-cell function, and they have an approximate 10% incidence of diabetic retinopathy. By both pathophysiological and clinical standpoints, these pre-diabetic individuals with IGT should be considered to have Type 2 diabetes” (emphasis mine).
The takeaway from this is Dr. DeFronzo’s main point: We need a “new paradigm” of early intervention: “The clinical implications of these findings for the treatment of Type 2 diabetes are that the physician [my emphasis] must intervene early, at the stage of IGT [impaired glucose tolerance] or IFG [impaired fasting glucose].”
I am writing this blog primarily for patients in the hope that they will see the need to “intervene early” as well. It is so much easier to control your blood sugar if you have maximal insulin sensitivity and remaining beta cell function. 
DeFronzo begins, “Individuals destined to develop Type 2 diabetes inherit a set of genes from their parents that make their tissues resistant to insulin”  “In liver, the insulin resistance is manifested by an overproduction of glucose during the basal state despite the presence of fasting hyperinsulinemia and an impaired suppression of hepatic glucose production in response to insulin, as occurs following a meal.” (Translation: The liver overproduces glucose while we are fasting despite low blood insulin levels. That is why physicians now prescribe Metformin first to both suppress this unwanted glucose production -- called gluconeogenesis – and improve insulin sensitivity.)
“In muscle, the insulin resistance is manifest(ed) by impaired glucose uptake following ingestion of a carbohydrate meal and results in postprandial hyperglycemia.” “Both obesity and decreased physical activity are insulin resistant states and, when added to the genetic burden of insulin resistance, place a major stress on the pancreatic β-cells to augment their secretion of insulin to offset the defect in insulin action.” (Translation: insulin production increases to deal with both elevated levels of circulating glucose and our impaired insulin action due to insulin resistance.)
And here’s the crux of it: “As long as the β-cells are able to augment their secretion of insulin sufficiently to offset the insulin resistance, glucose tolerance remains normal.” (We have two faulty mechanisms at work here yet our blood glucose levels in response to both fed and fasting states are still NORMAL.) “However, with time the β-cells begin to fail and initially the postprandial plasma glucose levels and subsequently the fasting plasma glucose concentration begins to rise, leading to the onset of overt diabetes.” (Note: postprandial blood sugars rise first, then later fasting blood glucose.) That is the reason that the A1c test has replaced the fasting blood glucose test. The A1c test measures the average of all blood glucose values over a 3-month period and thus captures the elevated postprandial values in the average. Ask your doctor to do an A1c test. Medicare pays for 4 tests per year.)
“Collectively, the insulin resistance in muscle and liver and β-cell failure have been referred to as the triumvirate.” “The resultant hyperglycemia [elevated blood glucose] and poor metabolic control may cause further decline in insulin sensitivity, but it is the progressive β-cell failure that determines the rate of disease progression.
Dr. DeFronzo’s paper then continues to describe his own research into the β-cell failure rate in detail but let this suffice: “Although the plasma insulin response to the development of insulin resistance typically is increased during the natural history of Type 2 diabetes, this does not mean that the β-cell is functioning normally. To the contrary, recent studies from our group have demonstrated that the onset of β-cell failure occurs much earlier and is more severe than previously appreciated.” That frightening statement is in plain English. I don’t think it requires any translation or interpretation on my part. We (doctors and patients) need a “new paradigm” of early intervention.

Friday, May 24, 2019

Retrospective #98: The “Dreaded Complications” of Type 2 Diabetes


With the meteoric rise in the incidence of Type 2 Diabetes and obesity (“diabesity”, a cool conjunction), and their associated public health implications, the “dreaded complications” of the pandemic should now be front-and-center in the news. They do deserve our attention. They are pretty scary, and fear is a good motivator.
Here’s a truthful note from the American Diabetes Association: “Diabetes increases your risk for many serious health problems. The good news? With the correct treatment and recommended lifestyle changes, many people with diabetes are able to prevent or delay the onset of complications.” This would actually be a gross understatement, except for their use of the word “recommended.” Their “recommended” changes won’t work.
I would say that a Type 2 who follows a Very Low Carbohydrate diet can avoid the complications altogether. However, if you do not control your blood sugar by diet or other means, the NIH’s Medline Plus site tells us: “If you have diabetes, your blood sugar levels are too high. Over time, this can cause problems with other body functions, such as your kidneys, nerves, feet, and eyes. Having diabetes can also put you at a higher risk for heart disease [and] skin problems, digestive problems, sexual dysfunction, and problems with your teeth and gums.”
The order of magnitude of the risks of complications of chronic Type 2 diabetes are described in a Wikipedia entry:  In the developed world, diabetes is the most significant cause of adult blindness in the non-elderly and the leading cause of non-traumatic amputation in adults, and diabetic nephropathy is the main illness requiring renal dialysis in the United States” (emphases all mine). All of these complications are directly associated with Type 2 diabetes, and they are all the result of damage to the small blood vessels. These complications are all described as microvascular.
Today the main complications of chronically elevated blood glucose are macrovascular disease, which leads to cardiovascular disease (CVD). Wiki lists the following examples: Coronary artery disease (CAD), leading to angina or myocardial infarction (“heart attack”); diabetic myonecrosis (“muscle wasting”); peripheral vascular disease, which contributes to intermittent claudication (exertion-related leg and foot pain); and stroke (mainly the ischemic type).
In addition, Diabetic encephalopathy, the increased cognitive decline and risk of dementia – including Alzheimer’s disease – is observed in and associated with chronically elevated blood sugar, i. e. inadequately controlled Type 2 diabetes. These are just some of the risks, but I said I wasn’t going to scare the bejesus out of you. I guess I lied.
An abstract presented at a poster session at a 2012 ADA meeting is apt. It reported a Swedish observational study of 12,359 patients with poorly controlled Type 2 diabetes. None of the patients had any cardiovascular or coronary heart disease at baseline. The patients averaged 62 years of age with mean disease duration of 9 years. The average baseline A1c was 7.8% and their mean body mass index was 30. Their mean blood pressure was 140/78. 62% were taking antihypertensive (blood pressure) meds and 46% were on lipid-lowering (cholesterol) drugs.
After 5 years, the study’s investigators separated the patients into 2 groups: those whose A1c decreased by at least 1% over the 5 years (6,841) and those whose A1c remained stable or increased (5,518). At the study’s conclusion the mean A1c was 7% in the improved-control group (-0.8%) and 8.4% in the poorly controlled group (+0.7%). By then, 12% of the well-controlled group and 20% of the poorly controlled group had developed coronary heart disease (CHD). Cardiovascular disease (CVD) was present in 17% of those in the well-controlled group and 30% of the poorly controlled group. And all-cause mortality was 15% among the group with no improvement in A1c and 10% in the group with improved A1c. Thus, after adjusting for baseline risk factors during the study period, they concluded that “patients who had suboptimal glycemic control and reduced their A1c value by slightly less that 1% were 50% less likely to die within 5 years than were patients whose A1c did not improve.” Wow! A1c down <1%.
So, with an improvement in A1c of less than 1% (7.8 to 7.0%), there is still a 50% benefit. I wonder what the benefit would be for a 2% improvement in A1c? Would the increased risk of cardiovascular disease, coronary heart disease, and all-cause mortality be eliminated completely? That’s something you might want to think about.

Thursday, May 23, 2019

Retrospective #97: Fructose in Food

Fructose is commonly thought to be “fruit sugar.” And fruit is generally thought of as a “healthy” food, since it is “natural” (although hybridized to be made sweeter). It has fiber, pectin, micronutrients and phytochemicals, all of whose mysteries we have yet to unwrap. Still, we consider them all beneficial. As a result, there is a widely held perception that since all fruit contains “natural sugars,” it is therefore okay to eat whole fruit in moderation. Besides, who can eat a dozen apples? True enough, except: watch out for apple sauce and apple juice. These two highly processed apple food products are very high in liquefied sugars and especially high in fructose. Pears too.
But fructose, the “natural fruit sugar,” is not just found in fruit. It is present naturally in many other whole foods. Fructose is 40% to 67% of the sugar in fruits, from 38% to 55% of the sugars in some vegetables, and 49% to 82% of the sugar in sweeteners, both natural and manufactured.  Fructose is 50% of the content of granulated sugar, made either from sugar cane or sugar beets. And fructose is 55% of the liquid form of high fructose corn syrup (HFCS) used to sweeten soft drinks in the U.S. HFCS is also used for a variety of other reasons in solid foods, including “mouth feel.” In a loaf of bread, it is brushed on the surface to brown it when baked and to get those whole grains to stick. The HFCS used in baked goods and many more products is a special type that is only 42% fructose.
The table below, created from USDA and Wiki sources, lists common “foods,” including fruits, vegetables and sweeteners (natural, refined and manufactured). It is sorted by total percent fructose.
Sugars in Foods
Sucrose
Free
Free
Other
Total
Total
Fructose/
as % of total sugars
50%F/50%G
Fructose
Glucose
Sugars
Fructose
Glucose
glucose ratio
agave nectar
0%
82%
18%
0
82%
18%
4.47
pear
8%
63%
29%
0
67%
33%
2.06
apple
20%
57%
23%
0
67%
33%
2.01
water melon
20%
55%
26%
0.06
64%
36%
1.81
HFCS55 (beverages)
0%
55%
41%
4%
57%
43%
1.34
sweet red pepper
0%
55%
45%
0
55%
45%
1.21
honey
1%
53%
46%
4.54
53%
47%
1.14
grapes
1%
52%
46%
0
53%
47%
1.12
pineapple
61%
21%
17%
0
52%
48%
1.09
molasses
54%
24%
22%
0
51%
49%
1.03
Granulated sugar
100%
0%
0%
0%
50%
50%
1.00
beet sugar
100%
0%
0%
0%
50%
50%
1.00
brown sugar
97%
1%
1%
1%
50%
50%
1.00
red beet
97%
1%
1%
0
50%
50%
1.00
carrot
75%
13%
13%
0
50%
50%
1.00
popcorn
69%
16%
16%
0
50%
50%
1.00
banana
20%
40%
41%
0
50%
50%
0.98
maple syrup
96%
1%
3%
0
49%
51%
0.96
dried fig
0%
48%
52%
0
48%
52%
0.92
sweet onion
14%
40%
46%
0
47%
53%
0.89
peach
58%
18%
24%
0
47%
53%
0.89
sweet potato
60%
17%
24%
0
46%
54%
0.87
HFCS42 (solid foods)
0%
42%
53%
5%
44%
56%
0.79
apricot
64%
10%
26%
0
42%
58%
0.72
plum
16%
32%
52%
0
40%
60%
0.66
sweet corn
15%
31%
55%
0
38%
62%
0.61
After agave nectar (82% fructose), pears and apples are the worst (2/3rds fructose). And natural sweeteners like honey and maple syrup are about half fructose, and they aren’t even fruit! Only corn is low, but higher in glucose.