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Thursday 1 November 2018

Dietary Carbohydrate Restriction in The Treatment of Diabetes and Metabolic Syndrome

Dietary Carbohydrate Restriction in The Treatment of Diabetes and Metabolic Syndrome

Richard D. Feinman, PhD, Jeff S. Volek, PhD, RD and Eric C. Westman, MD 
Learning Objective:
After reading this article, the participant should be able to:
1. Understand in broad outline the benefits of carbohydrate restriction for diabetes and metabolic syndrome.
2. Have awareness of the literature studies on low-carbohydrate diets for the treatment of diabetes.
3. Discuss with patients the resources and information available for diets stressing carbohydrate restriction.
Dr. Feinman is Professor of Biochemistry at the State University of New York Downstate Medical Center, Brooklyn, NY 11203; Dr. Volek is Associate Professor of Kinesiology at the University of Connecticut, Storrs, CT  06269-1110; Dr. Westman is Professor of Medicine at Duke University School of Medicine, Durham, NC 27704 ; e-mail:rfeinman@downstate.edu
The authors have disclosed that they have no significant relationships with or financial interests in any commercial organizations pertaining to this educational activity.
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Word count text = 2004
Diabetes is fundamentally a disease of carbohydrate intolerance.  Reduction in dietary carbohydrate, alone or as an adjunct to pharmacology, is thus an intuitive approach to treatment.  The major therapy before the discovery of insulin, low carbohydrate diets are perceived as part of diabetes therapy by many physicians and laymen alike. Since the discovery of insulin, however, the standard diet has emphasized fat reduction and health agencies have specifically discouraged the use of low carbohydrate diets although the American Diabetes Association (ADA) (1) has recently given limited acceptance, at least for weight loss.
It has also been argued that carbohydrate restriction improves all the features of metabolic syndrome and, as such, provides an operational definition (2) as well as a treatment modality, an idea supported by prospective studies(3).
For the practitioner contemplating the use low-carbohydrate diets, there is a need to understand the basic rationale for a course of action different from standard recommendations.  Guidance on implementation is also required, especially for patients already on medication where one has to avoid the risk of hypoglycemia due to the combined effects of drug and diet.
CASE STUDY – TYPE 2 DIABETES MELLITUS
DN, a 56 y/o Caucasian male presented with a 3 year history of type 2 diabetes, coronary artery disease, hyperlipidemia, hypertension, gastroesophageal reflux disease, sleep apnea, and depression. His weight was 131.1 kg, BMI 41.4 kg/m 2.  Blood glucose varied from 130 to 390 mg/dL and hemoglobin A1c was 8.2%.
Medications included Lantus insulin 46 units daily, Byetta 5 mcg twice daily, glipizide 10 mg twice daily, Nexium 40 mg daily, Toprol 100 mg daily, Enalapril 20 mg daily, Cymbalta 40 mg twice daily, Lyrica twice daily.
DN was started on a carbohydrate-restricted diet (< 20 grams/day) and followed at 1-2 weeks intervals to monitor adherence and medications. Because reductions in dietary carbohydrate allow return to more normal glycemic control and reduced insulin fluctuations, insulin and other glucose-lowering  drugs must be reduced in advance. Upon program initiation, DN’s Byetta was discontinued, insulin was reduced to 30 units but glipizide was continued.   After two weeks,  blood glucose was 94 to 172 with several readings below 100 mg/dL and  insulin was discontinued. By the fourth month DN had only been able to reduce his weight by 8 % to 120.6 kg (BMI 38.1 kg/m2), but blood glucose was 111 to 156, (HbA1c =5.7%) and he was able to discontinue all medication.
RATIONALE FOR CARBOHYDRATE RESTRICTION
Several reports in the scientific literature, consistent with the case study, provide support for low-carbohydrate diets as an attractive alternative if not the preferred treatment in diabetic and pre-diabetic states (4) A recent small study has been followed to 44 months (5).
These reports were summarized in a multi-authored paper  that laid out the basic features of low-carbohydrate diets (6).  The major principles emphasized were:
1. Carbohydrate restriction improves glycemic control, the primary target of nutritional therapy and reduces insulin fluctuations.
2. Carbohydrate-restricted diets are at least as effective for weight loss as low-fat diets.
3. Substitution of fat for carbohydrate is generally beneficial for markers for and incidence of CVD. Whereas low-fat diets are generally more effective for reducing LDL, dietary carbohydrate is the strongly correlated with small dense LDL which are considered more atherogenic and carbohydrate restriction is the most effective method of lowering triglycerides and raising HDL.
4. Carbohydrate restriction improves the features of metabolic syndrome.
5. Beneficial effects of carbohydrate restriction do not require weight loss.
Points 2 and 5 are of particular importance in that the 2008 ADA Recommendations and Interventions (7) received some attention for admitting, for the first time, that “for weight loss, either low-carbohydrate or low-fat calorie-restricted diets may be effective in the short term (up to 1 year).”  The emphasis on weight loss rather than glycemic control seems odd to many but given how difficult it is to lose weight by any method, patients and physicians should be encouraged by the fact that benefits accrue to low-carbohydrate diets even if weight reduction is not attained .  Experiments in the literature have demonstrated dramatic improvements in triglycerides and HDL-C in patients with type 2 diabetes under conditions where reduction in body mass were minimal(8).
PRACTICAL CONSIDERATIONS – MEDICATIONS
It is frequently suggested that lifestyle interventions are as successful as pharmacology in treating diabetes, but traditional lifestyle changes stressing high carbohydrate have the potential for increasing the need for drugs.  The 2008 ADA Recommendations contain the telling statement(9):
“Sucrose-containing foods can be substituted for other carbohydrates in the meal plan or, if added to the meal plan, covered with insulin or other glucose lowering medications. Care should be taken to avoid excess energy intake.”
One of the ironies in this recommendation is that insulin therapy is established to pre-dispose to weight gain(10).  Patient apprehension of the possibility of insulin-related weight gain has been cited as a barrier to insulin use(11).
Reduction in medication is sensibly taken as improvement in a medical condition.  The case study above is characteristic of the carbohydrate-restriction interventions and remains one of their strongest benefits(12). At the Duke Lifestyle Clinic, using diets of 20 grams carbohydrate maximum per day (VLCKD; Table 1) it has been possible to have patients taper off as much as 280 units of insulin in 3 weeks.  Because  there is  immediate improvement in glycemic control, patients already on glucose-lowering drugs must have medication reduced or eliminated before a change in diet. Blood pressure also improves, so patients taking antihypertensive medication require monitoring as well.
METABOLIC SYNDROME
The concept of a metabolic syndrome (MetS; insulin resistance syndrome) has had great intellectual impact in medicine because it suggests that a broad and seemingly disparate set of conditions of overweight, hypertension, atherogenic dyslipidemia (high triglycerides and small dense-LDL-C and low HDL-C) have a common origin.  The underlying factor is likely insulin resistance, simultaneously a feature of the diabetic or pre-diabetic state.  Recent papers in this journal and others have raised the question as to whether the concept is really useful for the clinician (13). That is, would characterization of multiple markers as a syndrome lead to any different treatment than the sum of the treatments for each individual risk indicator?
The observation that traditional and emerging markers of MetS are precisely those that are targeted by carbohydrate restriction provides evidence for the appropriateness of the designation syndrome and suggests, as well, a unique method of treatment (14).  Thus, there are many ways to treat obesity but none are as effective as carbohydrate restriction at improving triglycerides.  Known since the fifties (15) this is probably the most robust response to any dietary intervention, Similarly, there are several pharmacologic approaches to raising HDL-C or improving hypertension but few target the other markers.  In addition, low-fat diets tend to lower HDL-C and, in any case, seem to require weight loss for beneficial effects whereas carbohydrate restriction does not.  Carbohydrate restriction is also of obvious value in improvement of glycemic and insulin responses which are frequently exacerbated by low-fat diets.
That the collection of markers is improved by a single type of intervention argues for the existence of a common (carbohydrate-sensitive) mechanism and suggests for the physician that treating any one marker by reducing carbohydrate has the potential to prevent the onset of others which may not be evident at the moment. This hypothesis was tested in a prospective study in which forty overweight subjects with atherogenic dyslipidemia were randomly assigned to dietary interventions restricted in fat (low fat diet, LFD) or carbohydrate (carbohydrate-restricted diet, CRD).  Subjects consuming the CRD had improved glycemic control and insulin sensitivity, greater reductions in weight and adiposity and improvements in several inflammatory markers(16).
CASE STUDY – METABOLIC SYNDROME
L.G. is a 48 y/o Caucasian male with MetS. He was taking no medications and was started on a carbohydrate-restricted diet (<20 grams/day) and followed every 1-2 months to reinforce adherence for a 12 month period.  No medication was instituted.  Results were as follows:
Baseline12 months
serum triglyceride (mg/dL)473218
blood glucose (mg/dL)11792
waist circumference(cm)11199
blood pressure (mm/Hg)128/81125/80
body weight(kg)110.898.4
BMI(kg/m2)31.327.8
PRACTICAL CONSIDERATIONS – WHAT TO EAT
Implementation of low carbohydrate diets is complicated by the lack of clear definitions.  Many studies show benefits proportional to the reduction in carbohydrate but there also appears to be a threshold effect reflected in the recommendation for very low carbohydrate diets, the so-called induction period of popular diets such as the Atkins Diet.  Table 1 lists definitions which would probably be accepted by most workers in low carbohydrate diets.
Carbohydrate-restricted diets do not generally specify what  the carbohydrate is to be replaced with leading critics to characterize them as high-fat or high-protein.  LaRosa was the first of several researchers to show that in practice, many dieters simply reduce calories by removing carbohydrates without replacement (17).  Protein in the diet generally tends to be relatively stable and the key question is the relative amounts of fat and carbohydrate.  According to the rationale for carbohydrate restriction, where  glucose and insulin are control elements, fat is expected to play a relatively passive role and specific recommendations to reduce fat are unnecessary. Undesirable effects of high fat are seen only under conditions where carbohydrate is moderate to high and, in any case, substitution of carbohydrate for fat is almost always deleterious (18).
A survey of an online support group, the Active-Low Carber Forums showed, perhaps surprisingly, that the major change for dieters was increase in the consumption of non-starchy vegetables (19). Low-carbohydrate diets may in some sense be characterized as high-vegetable diets.  Finally, although critics of low carbohydrate diets point to limited choices, there are now thousands of recipes and strategies on the Internet, the most comprehensive is probably the site at About.com (http://lowcarbdiets.about.com/).
PRACTICAL CONSIDERATIONS –  EXERCISE
Exercise clearly enhances the proportion of fat loss, especially if the exercise involves resistance training. The combination of resistance training and diet has been investigated in two studies which both showed that men and women who consumed a low carbohydrate diet while performing resistance training 3 times per week had the greatest decreases in percent body fat (20).
PRACTICAL CONSIDERATIONS – COMPLIANCE
Side effects and, conversely, the ability to realize therapeutic goals strongly affect adherence to any intervention but compliance with a diet is largely separate from the efficacy of the diet itself and depends on the motivation, external support and the overall features of the patient-physician interaction.  Low-carbohydrate diets attain at least as high a degree of compliance as low fat diets in experimental trials but such experiments may not offer the full potential for patient support.
The internet provides opportunity for support of people attempting to follow a low carbohydrate diet.  The Active-Low Carber Forums (http://forum.lowcarber.org/ ) as of September, 2008 had more than 110, 000 members.  The forums and similar support groups specifically targeting people with diabetes offer support and suggestions for implementing dietary plans. The widespread use of glucometers suggests that people with diabetes my have a unique opportunity to participate in their own medical nutrition therapy.  Education and support from physicians will be most successful in patients who are able to discover for themselves which foods or combinations of food will allow good glycemic control.
SUMMARY
In treating patients already receiving medication, physicians may need training in the use of low-carbohydrate diets but the literature and case studies are consistent with the intuitive value of such diets.

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