Low Carbohydrate Lifestyle Reduces Significantly Insulin Need in Type 2 Diabetes Patients Diabetes

A low carbohydrate diet is suggested to be effective in type 2 diabetes to reduce or stop glucose lowering medication. To prove the effectiveness of this dietary change, a low carbohydrate diet was studied in patients with type 2 diabetes on the amount of insulin, HbA1c values and weight loss. Methods An observational study in one dietitian practice on the treatment of patients with type 2 diabetes, all on an insulin regimen, with a low carbohydrate diet. Two HbA1c values prior to, and after six months of the dietary intervention were measured. All patients received a dietary advice to consume 30 grams carbohydrates per day in a day menu schedule. Patients visited the outpatient clinic to discuss their results, experiences, and questions. The online treatment group received feedback every week and extra support per mail. Results We included 37 overweight type 2 diabetes patients on insulin treatment and evaluated 35 patients after 6 months. The consumption of carbohydrates was 31±10 grams per day. Insulin use was reduced significantly (p<0.001) from 62.6±46.4 IU to 1.4±6.4 IU per day. For 92% of the participants, insulin injections could be stopped completely. Patients lost a mean of 13.3±6.3 kg of weight and the mean HbA1c level declined from 63.4±11.0mmol/mol to 56.9±13.0mmol/mol (p<0.001). Conclusion A low carbohydrate dietary lifestyle is effective in improving HbA1c and weight loss and leads to a significant reduction of insulin need.


IOD.000591. 4(4).2020
interventions are crucial. Most diabetes guidelines primarily recommend starting with nutritional and physical activity lifestyle changes to reduce weight [7,8] and secondly if this fails, starting pharmacotherapy. In daily practice, more than 73% of the patients start with pharmacotherapy [9] because they fail to make changes in lifestyle and diet, and do not achieve weight loss.
Insulin is added to oral medication in a considerable number of patients (24%) [9] with T2DM because oral glucose lowering drugs do not lead to acceptable glucose and HbA1c levels.
However, treating blood glucose levels is not going to prevent the development of vascular pathology in diabetes. This was confirmed in seven multinational, multi-center, randomized controlled trials of tight blood glucose control with medications (ACCORD, ADVANCE, VADT, ORIGIN, ELIXA, TECOS and SAVOR) [10][11][12][13][14][15][16]. They all failed to demonstrate reductions in heart disease, the major cause of death of persons with diabetes [17]. The

18-country observational Prospective Rural Urban Epidemiology
(PURE) Study concluded that the total fat intake and types of fat (saturated, mono-unsaturated, poly-unsaturated) in a diet were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality [18]. The biggest problem of diabetes pharmacotherapy with sulphonylureas and insulin is that it causes weight gain [19]. Weight gain is undesirable because 90% of patients with T2DM are overweight or obese already [19].
Weight gain and the development of atherogenesis is caused by the physiological role of insulin as an anabolic hormone. It plays a role in the conversion of carbohydrates (CH) into body fat. The more carbohydrates T2DM patients eat, the more fat synthesis insulin gives especially in those who are insulin resistant which is characterized by hyperinsulinemia. Guidelines advise patients to eat on average 150-250 grams of CH a day [20,21]. Because CH promotes insulin release, which causes fat storage, the advised amount of CH might not be ideal and even be counterproductive. Studies in which the amount of CH intake was reduced showed an improvement of T2DM [22][23][24][25][26][27][28][29]. Reducing CH intake is not only causing weight loss but also a decrease in IR. The hypothesis is that by introducing a CH low lifestyle in T2DM patients, glucose levels normalize, and weight loss will be achieved, resulting in a diminishing need for exogenous insulin. Therefore the aims of this study were to investigate the effects of a low carbohydrate diet on insulin need, HbA1c levels and bodyweight in patients with T2DM treated with oral medication and insulin therapy.

Study design
An analysis of retrospectively collected data from a group of T2DM patients taking a low CH diet that were on oral and insulin therapy. The data was collected from one dietary practice (Prima Vita, Buren, the Netherlands) that is specialized in the treatment of patients with T2DM during the period January 2016 to April 2017.
The dietitian also has more than 25 years of experience as a trained nurse diabetes specialist.

Selection participants
We included 37 participants who met the inclusion criteria of: age between 18 to 75 years, T2DM on oral and insulin treatment, overweight (BMI>25kg/m2) and/or an abdominal circumference of ≧80cm in females and ≧102cm in males. Exclusion criteria were pregnancy and renal failure defined as calculated serum glomerular filtration rate under 30ml/min. Cardiac patients with heart failure and psychiatric patients with lithium medication were also excluded.

Dietary intervention
For motivation to join the low CH diet, all participants were informed about the relationship between carbohydrates, IR and the effects on metabolism, the amount of insulin needed and weight loss, that was found in scientific publications [23][24][25][26][27][28][29]. All patients had previously followed a low fat, high CH diet without improvement of the T2DM or weight loss. In a shared decision setting, patients freely chose to start with the low CH diet. Then, participants were instructed how to follow a low CH diet and encouraged to keep the CH intake between 30 and 50 grams a day, preferably around 30 grams a day. To achieve this, they were instructed to leave out products rich in CH like rice, pasta, potatoes, fruits and replace normal bread with low carb bread. They were advised to take a zero CH breakfast or up to 5 grams CH maximum. This was achieved by eating, for example, eggs, cheese and vegetables. Patients received a dietary advice in the form of a day menu. Furthermore, booklets with background information were provided. They were encouraged to ask questions to support them on the diet.

Tapering off T2DM medication
On the same day patients started making the dietary changes, the insulin dosage was stopped completely if the total amount of insulin was up to 30 IU. Insulin was lowered by half if the total amount of insulin was over 30 IU and lowered according to the scheme ( Figure 1). In the first two days after tapering off or stopping insulin injections, the serum glucose levels were communicated by phone and if necessary, the medication was adjusted. Thereafter, a weekly based follow up by phone or email was organized. More frequently, when participants had questions or were uncertain about their serum glucose levels, a quick answer was provided. The first target was to stop the long term insulin therapy because this has most side effects on weight gain. Every one to two weeks, insulin therapy was lowered, and this was repeated until all insulin finally could be stopped when 10 or less IU daily therapy was achieved ( Figure 1). For patients, seeing the result of using less or no insulin was a big motivational factor to continue with the low CH diet. For this reason, it was chosen to start the low carbohydrate diet from one day to another instead of lowering carbohydrates in phases. As soon as weight loss stagnated, or hypoglycemic episodes occurred, insulin was also lowered again. Next, when still on sulphonylureas, we started to taper and stop these oral drugs after stopping insulin also.

Monitoring
For follow-up, some of the participants visited the dietitian practice on a frequent basis, but most of them were monitored online via the dietitian's own website, where they had an account [30]. They stayed in touch with their own physicians or diabetes nurses for their regularly scheduled check-ups. We measured weight, BMI, waist circumference, HbA1C and the amount of insulin used at baseline and after six months. All therapy changes and additional information was reported in participants files.

Statistical analysis
Changes in insulin, HbA1C, body weight and carbohydrate intake were analysed using paired t-tests. Differences were considered significant at p<0.05. Values reported are mean  SD. After that, phase out the long term insulin, followed by the short lasting insulin. In case 8 IU or less are left then you can stop insulin totally after a few days. Goal is to stop all SU medication and insulin.

Results
Patient characteristics are summarized in (Table 1).
Carbohydrate intake in all participants during the study period was 31±10g/day. Patients did not significantly change their physical activity during the diet period.

HbA1c
The HbA1c levels were decreased significantly (p<0.001) from 63.4±11.0 at start, to 56.9±13.0mmol/mol after six months ( Figure   2). In 29 out of 37 patients, a decrease was found; in four patients, the levels were unchanged and in six, levels increased.

Body weight
Mean body weight of the participants decreased from 97.8±18.1 to 84.5±15.2kg (p<0.001). This is a mean weight loss of 13.3kg (-13.5%). In 3 participants, body weight after six months was unknown ( Figure 3).

Carbohydrate intake
Carbohydrate intake in all participants during the study was 31±10g/day. There were participants who themselves lowered the carbohydrate intake to 15-20g/day.

Discussion
This observational study showed that a low CH diet in T2DM patients on oral and insulin therapy was able to reduce insulin This led to an increase in IR and thereby a higher need for more insulin. We suspect that T2DM patients are CH intolerant because of insulin resistance (IR). Weight loss is crucial for a better T2DM management because it decreases IR. The decrease in IR also has a positive effect on lowering the systemic inflammation that plays a role in comorbidities like cardiovascular disease, hypertension, dyslipidemia, kidney failure and NAFLD [5,6,29]. Taken together, lowering CH intake and stopping insulin injections while losing weight, improves T2DM more than sticking to guidelines that advise eating high CH [21,22] and adding diabetes medication. Considering the fact that most of our patients reached that objective, we argue that treatment of these patients, of whom 90% were overweight or obese, include lowering or stopping weight promoting medication, supported by a low CH lifestyle. Another aspect in the management of T2DM is the long term control by measuring HbA1c. From experience over a long period of diabetes care, HbA1c and glycaemia improved when insulin dose increased, resulting in weight gain. In this study, a significant reduction of the HbA1c levels ( Figure 3) was documented, although the study period of 6 months was rather short to evaluate the long term effect on glucose blood levels and diabetes control. Patients did not experience hyperglycemia complaints but did have a better health and much more energy. These results indicate that a change in the diabetes type 2 treating protocol should be considered.
We should reconsider what should be treated: blood sugar levels and thus only symptoms, as we are doing now in conventional diabetes treating protocols, or the metabolic aspects. The results of our short time, small study, are similar to results of Virta Health [27]). They found that after 1 year, compliance to a very low CH lifestyle (less than 30 grams a day), was 85 %. This is higher than pharmacotherapy compliance with T2DM medication [7,9,23]. it is hard to resist them. This makes it probably harder to keep the diet for many years. More is needed to raise the awareness in policy makers and the food industry that large quantities of carbohydrates are not only on individual level but also in society unwanted and harmful. Long term studies are necessary to proof the effect on the long run and how it affects the general metabolic health of patients and society. The lowering carbohydrate approach will certainly decrease health care costs and improve quality of life ( Figure 4).
Therefore, future studies should be initiating measuring a broad range of consequences related to a low CH lifestyle like metabolic, psychological, healthcare, quality of life and costs aspects. Since hyperinsulinemia is the central driver of fat storage in insulin resistance and the development of comorbidities that goes along with hyperinsulinemia, measuring endogenous insulin should be part of diagnosing diabetes type 2, to hopefully prevent them from getting on insulin therapy in the first place.

Conclusion
This study showed that a low carbohydrate dietary lifestyle of 31±10 g per day is effective in significantly improving HbA1c, weight loss and insulin need in T2DM patients on oral and insulin treatment. The Mindshift of not treating hyperglycemia but focusing on treating hyperinsulinemia was key. Applying this on a larger scale would result in more healthy patients and lower health care costs. These results indicate that more research, regarding this treatment method, has to be done on a larger scale, considering the impact it could have on the way diabetes type 2 is treated in modern society.