Weight reduction in patients with type 2 diabetes

Increased body weight and diabetes mellitus often go hand in hand. Even if the topic of weight reduction in patients with diabetes is often difficult and difficult to implement, it is worthwhile to work with patients on this point, because only through a (moderate) weight reduction can the disease be stabilized and possibly even brought into remission. The basics are realistic therapy goals with a sense of proportion and a long-term, multi-year therapy with various modules (medical care, nutritional counseling, psychological support, drug therapy). In case of increasing metabolic derailment with intensification of therapy and increasing body weight, surgical measures should also be discussed with the patient.

Obesity increases the risk of type 2 diabetes and cardiovascular disease [1]. The risk of diabetes in people with a BMI below 25 ^kg/m2 is about 4%, rising to 25% in those with high-grade obesity. For example, in women, a BMI above 30 kg/m2 is associated with up to a ninefold increased risk of developing type 2 diabetes (compared with normal-weight women) [2]. Therefore, it is not surprising that over 75% of patients with diabetes have concomitant overweight (BMI >25 ^kg/m2) or even obesity with BMI over 30 ^kg/m2 [3].

However, there seems to be some reversibility of events here. Weight loss, even if only moderate, can significantly improve the achievement of blood glucose and blood pressure targets and the adjustment of blood lipids, especially triglycerides and less cholesterol [4]. Greater weight loss may even put diabetes into remission [5,6].

Less medication thanks to weight reduction

The mass of beta cells decreases significantly over the course of life. This inevitably leads to the fact that the previous diabetic medication is no longer sufficient and the therapy must be intensified by adding further medications. By reducing weight, the therapy can be kept the same, and in the case of greater weight loss, medications already in use can even become completely unnecessary [4,6].

However, despite these beneficial effects, lower cardiovascular mortality was not demonstrated for patients with diabetes and moderate weight reduction. This was recently shown in a large study from the USA in over 5000 patients with type 2 diabetes [4]. Although there was no difference in cardiovascular events between the two treatment groups, positive effects were seen in the group with more intensive lifestyle modification and thus higher weight reduction. Among other things, they suffered less depression, they needed less medication, and sleep apnea syndrome and musculoskeletal complaints improved [4,7–9]. Weight reduction is therefore worthwhile! But why is it so difficult to achieve them and especially to maintain the lower weight?

Weight loss as an existential threat

To better understand the regulation of body weight, it is helpful to consider this point from the perspective of nature [10]. A stable or even slightly increasing body weight has always been an evolutionary advantage for the survival and preservation of the species [11]. Weight loss, on the other hand, is a sign of an existential threat. In such a phase the organism is protected and brought over the phase of food shortage. This happens through manifold changes in the body. In this way, the energy balance can be reduced, the hunger hormones increased and the intestinal flora modified in such a way that better energy utilization from the food consumed takes place [10–14].

Following the phase of food scarcity, compensation is made accordingly when unrestricted access to food sources is possible again [15]. Therefore, it is understandable that due to the increasing and constant availability of energy-dense foods, the development of obesity is an almost inevitable consequence.

Set realistic goals

Thus, weight reduction in patients with type 2 diabetes should be a long-term endeavor. Different measures can be combined with each other in a modular way. Initially, realistic weight goals must be formulated. A reduction of 3-4 kg in six months is realistic and feasible under everyday conditions. Guidelines often still include very high and unrealistic weight goals such as 10% weight reduction in 6-12 months for obese patients with diabetes. Without surgical measures or very-low-calories programs with a significantly reduced energy intake of, for example, 800 kcal per day, such goals can hardly be realized [16,17]. It also seems questionable whether such a strong initial weight reduction can be maintained in the long term and whether it does not only contribute to the frustration of patients and practitioners when weight increases again in the course of treatment [18].

Possible measures that can support weight reduction are, on the one hand, lifestyle programs that optimize patients’ exercise behavior and, on the other hand, nutritional counseling that analyzes and favorably influences eating behavior and food composition. However, the choice of diabetes medications and concomitant medications can also have a positive impact on patients’ weight. However, the basis is the long-term and regular monitoring of the patient. Mentioned modules can then build on this alternately or in combination. Studies have clearly shown that the intensity of care is crucial for success in weight loss [19]. Care can be provided through the interested primary care physician, endocrinologist, or nutritional therapist. Here, it is often decisive which person can develop the best access to the person concerned.

Combination of nutrition, exercise and behavioral therapy.

The foundation of any weight loss program is a combination of nutrition, exercise and behavioral therapy. The combination of these therapeutic approaches often produces greater weight success than individual measures. While a dietary change alone can lose an average of just 1.8 kg, the average weight loss with a combination of nutritional therapy and physical training is already 3.6 kg [16]. In general, the effects of group programs are greater than those of individual therapy. In addition, group sessions are often less expensive.

Weight management includes not only the phase of weight reduction, but also the phase of long-term stabilization of the achieved weight [18]. The weight treatment offered should be based on the patient’s resources. Involving family or friends shows a significant improvement in the results achieved, especially for women, and is critical for long-term compliance [16].

Change of diet

With regard to dietary changes, it should be noted that the desired energy deficit can be achieved by reducing the proportion of fat or carbohydrates, or a combination of both. The goal is an energy reduction of about 500 kcal per day. This allows an average weight reduction of 3-4 kg in a period of six months [17]. Weight loss is greater the higher the initial weight and previous fat consumption were [16].

Interestingly, diet type (high-carbohydrate/low-fat, high-protein/low-fat, high-fat, and high-fat/protein) does not seem to play a relevant role with regard to weight loss and improvement of concomitant risk factors [19]. Here, therefore, the preferences of the individual person can be taken into account. Extremely one-sided diets (e.g. total fasting or crash diets) are to be rejected on principle, since they involve unnecessary and incalculable risks and a justifiable benefit is not apparent. People with concomitant diseases are particularly at risk, which is often the case in patients with diabetes.

More movement

In addition to dietary changes, increased exercise plays an important role in the treatment of obesity. Increased energy consumption can result in a negative energy balance. In addition, exercise therapy has positive effects with regard to a number of obesity-associated diseases and increases the quality of life of those affected [7]. Increased exercise combined with an energy-reduced diet is considered the optimal lifestyle change for weight loss. For effective weight loss, one should exercise more than 150 minutes per week with an additional energy expenditure of 1200-1800 kcal/week [16,17]. Strength training alone is less effective for weight loss, so strength training should always be supplemented by endurance training [16].

Increased exercise, however, includes not only sports activity, but everyday activity in general. This can often increase daily energy consumption in a time-efficient manner [20]. Especially in the case of significantly increased body weight with a BMI >35 ^kg/m2 it is advisable to offer patients exercise programs that are not only fun but also relieve the musculoskeletal system (e.g. aqua jogging, aqua cycling etc.).

A good start to long-term weight loss is provided by the 12-week outpatient diabetes rehabilitation programs offered throughout Switzerland (www.diafit.ch).

Drug therapy for weight reduction

Drug therapy is not a primary form of treatment for overweight and obesity. Currently, only orlistat is available as a pure anti-obesity drug. In the ^XENDOS® study, patients with type 2 diabetes and a BMI around 37 ^kg/m2 achieved a placebo-corrected weight loss of 2.8 kg after four years [21]. However, this rather small weight loss is offset by therapy costs of a good 3 francs per day, corresponding to approx. 1200 francs therapy costs per year.

In patients with diabetes, however, we are currently in the fortunate position that some substance classes are available that, in addition to lowering blood glucose, can also reduce weight. In addition to the well-established metformin, the classes of SGLT 2 inhibitors and GLP 1 analogues have good weight-reducing potential. Metformin has been shown to result in a modest weight loss of approximately 2 kg, depending on tolerability and dose [22]. Similarly, the weight loss seen with SGLT 2 inhibitors [23].

GLP 1 analogues appear to have the strongest effect on body weight. You can reduce the weight by about 3-4 kg on average [24]. Large individual variations are often observed here; especially when switching from insulin, pioglitazone or sulfonylureas to a GLP 1 analog, more significant weight losses can sometimes be observed. This potential is also exploited by liraglutide, which has been approved by the EMA at a dose of up to 3 mg for weight loss (CAVE: in type 2 diabetes, the maximum dose is limited to 1.8 mg liraglutide). At the dose of 3 mg, weight reductions of up to 6 kg placebo-corrected have been observed in studies [25].

It therefore makes sense to switch the drug therapy for diabetes to the above-mentioned substance classes in patients who are striving to lose weight. It should be noted that a combination of SGLT 2 inhibitors and GLP 1 analogues should not be given at present.

Metabolic surgery

Over the past decade, the value of surgical options for the treatment of obesity and diabetes has increased. Underlying this development, among others, are randomized clinical trials comparing bariatric surgery with a combination of lifestyle intervention and optimal diabetes drug therapy in terms of weight loss and glucose metabolic control [26,27]. The studies show not only a significant weight reduction in the range of 20-40% of body weight, but also a massive improvement in metabolic control. This can be so pronounced that, depending on the surgical method, the patient can expect complete diabetes remission for years to come. Registry analyses also indicate that there is a positive effect on mortality in operated versus nonoperated patients [28].

The surgical measures represent an addition to the treatment options for type 2 diabetes. They should be considered if the patient’s weight is significantly increased (e.g., BMI >40 kg/m2) or if drug therapy without insulin is already well advanced and glycemic control is foreseeably worsening. In such cases, it is advisable to ask the question, “Where will the patient be in five to ten years?” In most cases, adding basal insulin and especially meal insulin accelerates the weight problem. Surgical intervention at this time can often put diabetes into remission [27]. Discussion with the patient about bariatric surgery is certainly indicated in such a situation. However, pursuing this option only makes sense if the surgery is conceivable for the patient and he or she can accept the changed life circumstances following the surgery.

After bariatric surgery, the patient requires lifelong, interdisciplinary follow-up care. This should be ensured by the operating center. Possible problems and complications after these interventions are manifold and certainly not yet fully understood in their entirety. Key points of follow-up care include monitoring of possible vitamin and mineral deficiencies and mental health, which may deteriorate as a result of the profound lifestyle and appearance changes.

Literature:

Mokdad AH, et al: Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003; 289(1): 76-79.
Weinstein AR, et al: Relationship of physical activity vs body mass index with type 2 diabetes in women. JAMA 2004; 292(10): 1188-1194.
Nguyen NT, et al: Relationship between obesity and diabetes in a US adult population: findings from the National Health and Nutrition Examination Survey, 1999-2006. Obes Surg 2011; 21: 351-355.
Look AHEAD Research Group: Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013; 369: 145-154.
Steven S, et al: Very-Low-Calorie Diet and 6 Months of Weight Stability in Type 2 Diabetes: Pathophysiologic Changes in Responders and Nonresponders. Diabetes Care 2016 Mar 21. pii: dc151942. [Epub ahead of print].
Winkler JK, et al: Effectiveness of a low-calorie weight loss program in moderately and severely obese patients. Obes Facts 2013; 6: 469-480.
Rubin RR, et al: Diabetes Care. Impact of intensive lifestyle intervention on depression and health-related quality of life in type 2 diabetes: the Look AHEAD Trial 2014; 37(6): 1544-1553.
Kline CE, et al: The Effect of Changes in Cardiorespiratory Fitness and Weight on Obstructive Sleep Apnea Severity in Overweight Adults with Type 2 Diabetes. Sleep 2016: 39: 317-325.
White DK, et al: Can an intensive diet and exercise program prevent knee pain among overweight adults at high risk? Arthritis Care Res (Hoboken) 2015; 67(7): 965-971.
Speakman JR: If body fatness is under physiological regulation, then how come we have an obesity epidemic? Physiology (Bethesda) 2014; 29(2): 88-98.
Sumithran P, Proietto J: The defense of body weight: a physiological basis for weight regain after weight loss. Clin Sci (Lond) 2013; 124(4): 231-241.
Johannsen DL, et al: Metabolic slowing with massive weight loss despite preservation of fat-free mass. J Clin Endocrinol Metab 2012; 97(7): 2489-2496.
Sumithran P, et al: Long-term persistence of hormonal adaptations to weight loss. N Engl J Med 2011; 365(17): 1597-1604.
Nadal I, et al: Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents. Int J Obes (Lond) 2009; 33(7): 758-767.
Purcell K, et al: The effect of rate of weight loss on long-term weight management: a randomised controlled trial. Lancet Diabetes Endocrinol 2014; 2(12): 954-962.
Wirth A, et al: Clinical practice guideline: The prevention and treatment of obesity. Dtsch Arztebl Int 2014; 111: 705-713.
American Diabetes Association: Standards of medical care in diabetes – 2016. Obesity Management for the Treatment of Type 2 Diabetes. Diabetes Care 2016; 39(Suppl 1): S47-S51.
Sumithran P, et al: Review of 3-year outcomes of a very-low-energy diet-based outpatient obesity treatment program. Clin Obes 2016 Feb 3. doi: 10.1111/cob.12135. [Epub ahead of print].
Sacks FM, et al: Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009; 360(9): 859-873.
Levine JA, Kotz CM: NEAT–non-exercise activity thermogenesis–egocentric & amp; geocentric environmental factors vs. biological regulation. Acta Physiol Scand 2005; 184(4): 309-318.
Torgerson JS, et al: XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized trial oforlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004; 27(1): 155-161.
Diabetes Prevention Program Research Group: Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care 2012; 35(4): 731-737.
Vasilakou D, et al: Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med 2013; 159(4): 262-274.
Aroda VR, et al: Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: meta-analysis and systematic review. Clin Ther 2012; 34(6): 1247-1258.
Pi-Sunyer X, et al: A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med 2015; 373(1): 11-22.
Schauer PR, et al: Bariatric surgery versus intensive medical therapy for diabetes-3-year outcomes. N Engl J Med 2014; 370(21): 2002-2013.
Mingrone G, et al: Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. Lancet 2015 Sep; 386(9997): 964-973.
Sjöström L, et al: Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007; 357(8): 741-752.