This article presents two studies that show the superiority of a healthy lifestyle in lowering cardiac-related deaths compared to diabetes medications. And second, the importance of managing early diabetes to prevent cardiovascular deaths.
The first study, Effects of voglibose and nateglinide on glycemic status and coronary atherosclerosis in early-stage diabetic patients, or the DIANA (DIAbetes and diffuse coronary NArrowing) study, was done in 2012.
It was designed to know what is better for decreasing coronary atherosclerosis in those with early diabetes.
Is it diet and exercise or diabetes medications?
The DIANA Study
The DIANA study examined 302 patients with coronary artery disease (CAD) and impaired glucose tolerance/diabetes mellitus (DM). They were assigned to three groups.
- Lifestyle intervention (n=101)
- Voglibose (0.9mg/day, n=100)
- Nateglinide treatment (180mg/day, n=101)
Voglibose and Nateglinide
Voglibose and Nateglinide are the diabetes drugs included in the study. Voglibose (Voglib) lowers after-meal blood sugar (post-prandial glycemia) by delaying glucose absorption. Glucose is the primary sugar resulting from carbohydrate digestion.
Voglibose is similar to Acarbose (Precose, Glucobay) and Miglitol (Glyset).
Nateglinide (Starlix) is a meglitinide that decreases blood sugar by stimulating insulin release from the pancreas. Insulin lowers blood sugar by making them enter the skeletal muscles, fat, and the liver.
Repaglinide (Prandin) is similar to Starlix.
Lifestyle Intervention
All participants were encouraged to start a low-calorie diet and mild to moderate exercise for at least 150 min per week. The aim is to achieve and maintain a weight reduction of at least 7% of the initial body weight.
Atherosclerosis Measurement
All had a coronary angiogram at the beginning of the year to know the presence and severity of any atherosclerosis in the arteries in the heart.
After a year, the coronary angiogram was repeated to see if the atherosclerosis were better or worse.
Blood sugar tests
Blood tests called the 75-g oral glucose tolerance test (75g-OGTT), fasting plasma glucose (FPS), and PPG or post-prandial blood sugar (blood sugar two hours after eating) were done to classify the patients based on their ability to handle sugar.
- Normal glucose tolerance (NGT) – Normal FPS, OGTT, and PPG
- Prediabetes or Impaired fasting glucose (IFG) – fasting plasma glucose (FPG) level <7.0mmol/L and a post-prandial glucose level PPG (120-min post-load glucose level) ≥7.8mmol/L but <11.1mmol/L or (≥100 and <126 mg/dL).
- Impaired Glucose Tolerance (IGT) – (FPG) level <7.0 mmol/L (126 mg/dl) and a PPG (120-min post-load glucose level) ≥7.8mmol/L (140.4 mg/dl) but <11.1mmol/L (199.8mg/dl).
- Diabetes Mellitus (DM) – FPG level ≥7.0mmol/L (126 mg/dl) and/or a PPG glucose level ≥11.1mmol/L (198 mg/dl).
Blood sugar status can change
Blood sugar states are not static. Anyone in the four categories, NGT, IFG, IGT, or DM, may change their condition with time.
A motivated person with DM can improve their blood sugar to progress to IGT and IFG and graduate into NGT.
Notice that NGT, IFG, IGT, and DM numbers changed after one year. All three groups started with similar numbers of IGT and DM.
After one year, all groups have higher numbers of NGT and lower numbers of DM. The OGTT (-) subjects did not continue with the study.
Improvements in blood sugar handling are good, but there is something more meaningful. The primary reason blood sugar is controlled is to lower the risk of cardiovascular disease.
Were there any changes in coronary atherosclerosis?
Changes in Coronary Atherosclerosis
After measuring the diameter of the arteries and the length of the atherosclerotic lesions in the arteries, they found that those who improved their glycemic status at the end of the year had improved coronaries.
In the table below, you can see that those with improved glycemic status (+) have lower Total Lesion Length (TLL), lower Average Aesion Length(ALL), and wider Average Vessel Diameter (AVD).
According to the authors, there were no significant differences in coronary atherosclerosis among the three groups at one year.
Compared to lifestyle intervention, voglibose and nateglinide did not slow coronary angiographic disease progression.
They conclude,
In the DIANA study, the effect of 2 pharmacological therapies on coronary atherosclerosis was comparable with that of lifestyle intervention, although voglibose significantly increased reversion to NGT at 1 year.
Importantly, regardless of the type of treatment, an improvement in glycemic abnormality (DM to IGT to NGT) was associated with less progression of coronary atherosclerosis in early-stage DM patients with CAD.
My Comment:
Since all eligible patients, including the ones on voglibose and nateglinide, were instructed to have a healthy diet and exercise, how much of the improvement in the blood test and coronary angiograms were attributable only to the drugs themselves?
In my previous article, Veggies Meat Carbohydrate Sequence Prevents After Meal Sugar Spike, eating vegetables first and then meat slows gastric emptying. Similar to the effect of voglibose.
While eating meat before carbohydrates stimulates insulin release before carbs like rice get into the stomach. The effect is similar to nateglinide.
Another way to decrease the after-meal blood sugar increase is to Walk After Meals to Prevent Sky-High Blood Sugar.
If the lifestyle group in this study ate using the vegetables-meat-carbs sequences and walked 15 to 10 minutes after their meal, more subjects should have had normal glucose tolerance.
Why is having normal glucose tolerance important? Because it lowers deaths from cardiovascular disease! This brings us to the second study.
DIANA Study – Ten years later
The study, Long-term effects of lowering post-prandial glucose level on cardiovascular outcomes in early-stage diabetic patients with coronary artery disease: 10-year post-trial follow-up analysis of the DIANA study, was published online on March 23, 2023.
It is a follow-up of 243 patients from the 2012 DIANA (DIAbetes and diffuse coronary NArrowing) study.
The DIANA patients took voglibose and nateglinide until 2008. After that, their doctors managed their diabetes medications. This year, 2023, a 10-year post-trial follow-up study was designed, resulting in this research.
Major Adverse Cardiac Events (MACE)
In the second study, the authors wanted to know how many had Major Adverse Cardiac Events or MACE. This includes cardiovascular deaths, a non-fatal heart attack, or an emergency coronary revascularization.
The number of cardiovascular deaths, which includes sudden cardiac death, death due to acute MI, heart failure, and stroke, was also measured in those with
- Abnormal fasting glucose or Pre-diabetes or impaired fasting glucose (IFG)
- Impaired Glucose Tolerance (IGT)
- Diabetes Mellitus
Pre-diabetes or impaired fasting glucose (IFG) is defined as an elevated fasting plasma glucose concentration (≥100 and <126 mg/dL).
Results
Compared to lifestyle intervention, lowering after-meal glucose rises or post-prandial glycemia PPG with voglibose or nateglinide was not associated with reducing major adverse cardiac events.
In addition, the frequency of all-cause death, non-fatal MI, and unplanned coronary revascularization did not differ among the three groups.
Lowering after-meal glucose spikes with voglibose or nateglinide did not reduce the occurrence of MACE in pre-diabetics and newly diagnosed type 2 diabetes mellitus subjects.
Pre-diabetic subjects who improved their glycemic status had lower cardiovascular events.
In contrast, lower cardiovascular events were not observed in newly diagnosed DM patients despite improving glycemic status (from DM to IGT or NGT).
The authors brought up the previous proposals of “metabolic memory” or the “legacy effect,” which states that earlier episodes of high blood sugar could have a long-standing impact on the future development of cardiovascular disease.
If you have diabetes, don’t be disheartened; many other pieces of research have shown that blood sugar control in people with diabetes still lowers premature cardiovascular events.
I have been researching metabolic memory and will probably write about it.
Conclusion
The two studies emphasize the necessity of diagnosing pre-diabetes and managing it immediately with lifestyle changes to prevent major adverse cardiovascular events.
Don’t give disease an inch. Diabetes is an existential threat. Fight it like your life depends on it.
That is why I always say, Don’t Get Sick!
Truth heals. Lies kill. Don’t Get Sick!
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Other ways to lower your atherosclerotic risk:
- Intermittent fasting Reverses Endothelial Dysfunction
- Walk After Meals to Prevent Sky High Blood Sugars
- After meal blood sugar spikes as a cause of vascular failure
- Veggies Meat Carbohydrate Sequence Prevents After Meal Sugar Spike
- Blood Glucose Spike and its Prevention
- Intermittent Fasting while on Diabetes Medications
- Yogurt and Intermittent Fasting Reduced Body Toxins
- Intermittent Fasting Grows New Liver Cells Faster
- The Fasting Experience of 1422 Subjects at the Buchinger Wilhelmi Clinic
- The Effects of Three-Week Fasting on the Extremely Obese
- The Effects of Intermittent Fasting on Asthma
- How to Do Intermittent Fasting
- The Kaizen Way of Fasting
- Early Time-Restricted Feeding is Intermittent Fasting In Sync with the Circadian Rhythm
References:
- Kataoka Y, et al. DIANA study investigators. Effects of voglibose and nateglinide on glycemic status and coronary atherosclerosis in early-stage diabetic patients. Circ J. 2012;76(3):712-20. doi: 10.1253/circj.cj-11-1011. Epub 2012 Jan 12. PMID: 22240597.
- Kataoka et al. Long-term effects of lowering post-prandial glucose level on cardiovascular outcomes in early-stage diabetic patients with coronary artery disease: 10-year post-trial follow-up analysis of the DIANA study. J of Diab and its Comp. https://doi.org/10.1016/j.jdiacomp.2023.108469
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