Before
the discovery of insulin in 1921, diabetic patients were treated by limiting
carbohydrate intake [1], which was viewed as both safe and effective. Elliott
Joslin, founder of the Joslin Diabetes Center, began using exogenous insulin in
1921/22 on some of his patients [2]. Once insulin became widely available it
displaced low carbohydrate diets (LCDs) in the mainstream medical community, in
large part due to Joslin’s success. Diabetic patients with insufficient
endogenous insulin secretion, e.g. type 1 diabetes (T1D), are generally treated
with insulin in modern times as well. This is quite logical as the deficient
substrate is directly replaced. Even when endogenous insulin is produced in
excess due to insulin resistance, insulin replacement is commonly utilized when
oral hypoglycemic agents (OHAs) and lifestyle modification are insufficient in
controlling blood glucose (BG). In the case of type 2 diabetes (T2D), dietary
modification is often recommended. Dietary focus in T1D tends to be primarily
limited to counting carbohydrates to estimate exogenous insulin requirements.
However, there are multiple reasons to encourage dietary modification as a
pre-emptive measure in T1D patients rather than an afterthought merely to
calculate insulin dosing. First, traditional diets restricting calories but not
carbohydrates are less effective than LCDs at good glycemic control. Second,
LCDs reduce quantitatively the requirement for antihyperglycemic medications.
In many cases, LCDs eliminate the need for any medication. Third, some symptoms
of metabolic syndrome improve. Some symptoms drastically improve within days of
LCD initiation. There is a plethora of definitions for LCD. Feinman and
Bernstein give tiered definitions of LCD [3]: i) Very low-carbohydrate ketogenic
diet (VLCKD), ii) Low-carbohydrate diet: <130 g/day or <26% total energy,
iii) Moderate-Carbohydrate Diet: 26%–45%, iv) High-Carbohydrate Diet: >45%.
We separate LCD into three tiers based on a percentage of total dietary
carbohydrate intake to aid in our scientific study. Super LCD, standard LCD,
and petit LCD are defined as 12%, 26%, and 40% of daily caloric intake from
carbohydrates, respectively [4]. The Japan Diabetes Society (JDS) is a major
health organization in Japan that focuses on diabetes care. The JDS recommends
that diabetic patients consume a calorie-restricted diet (CRD) high in
carbohydrates. We use a CRD that consists of 60% carbohydrate based on
historical recommendations when testing glycemic control. The protocol followed
at Takao Hospital is CRD on days 1-2 followed by super LCD on days 3-7 or 3-14,
depending on the length of the study. BG monitoring was initially solely by
glucometer, but CGM has recently been incorporated.
Super
LCD in T2D Patients
Case
1 is a 74-year-old male diagnosed with T2D 22 years ago. He had an HbA1c of
6.7% and a weight of 67 kg at the time of diagnosis. Within one month of
initiating the super LCD weight was decreased to 57 kg. HbA1c took months to
improve as expected and has been maintained at 5.7% after stabilizing. The most
recent labs in June 2023 are seen in (Table 1). No OHAs are used by this
patient. Case 2 is a T2D female in her 50s who had a Time in Range (TIR) of 60%
and 79% on days 1 and 2, respectively. TIR increased to 100% on day 6 and
continued at 100% to completion on day. Time below range (TBR) was 21% on day 1
but trended downward to 0% on day 6 where it remained until completion on day
14. This is evidence that decreasing carbohydrate intake decreases hypoglycemic
and hyperglycemic variability.
Case
3 is a male T2D patient in his 50s who saw improvements after starting a super
LCD. After just 7 months, HbA1c and weight down trended from 11.1% to 6.3% and
66 kg to 58 kg, respectively. After 7 years of super LCD HbA1c was 5.7 and
weight 57 kg. Figure 1 shows the changes in HDL, LDL, HbA1c, and body mass over
time.
Super LCD in SPIDDM Patients
Comparison
of 12 T2D subjects with positive Glutamic Acid Decarboxylase antibody (GADA)
(Group 1) versus 12 T2D subjects negative for GADA (Group 2) were conducted
using CRD 1-2 days and super LCD for days 3-14 [5]. Both groups performed
better as measured by meal tolerance test, post-prandial BG, and M value on the
super LCD. However, Group 2 had better glucose control than Group 1, which
could indicate progression to Slowly Progressive Insulin-Dependent Diabetes
Mellitus (SPIDDM) in GADA positive T2D patients.
Case
4 was found to be GADA positive and was diagnosed with SPIDDM in his 50s. He
has been treated with a super LCD alone for more than 4 years [6]. The
patient’s IRI has been 3.0 ?U/mL or less when measured. HbA1c has consistently
been maintained at 6.0% or less and FBG ranges from 90-111 mg/dL. The patient may
eventually require insulin. However, it appears that there is an increased
latency to insulin dependence that may be attributable to super LCD adherence.
Super
LCD in T1D Patients
Case 5 is a T1D patient in his 50s. After initiating
the super LCD, insulin requirements were reduced while markers of glycemic
control simultaneously improved [7]. CPR in January 2018 was 1.1 ng/mL and by
mid-2022 it had decreased to 0.2 ng/mL, indicative of declining but continuing
endogenous insulin production. This decline is associated with an increase in
insulin requirement; however, the patient still requires less insulin than
before starting the super LCD despite a decrease in CRP. In addition to
reducing insulin requirement, LCD could prolong endogenous insulin production.
Case 6 is a male in his 50s that was diagnosed with
T1D. He had a prolongation of the honeymoon phase by 16 months after the
continuation of the super LCD [8]. Additionally, this patient was evaluated
using the Takao Hospital protocol. TIR was 82% and 89% on days 1 and 2,
respectively. Afterward, TIR increased to 100% on day 8 and continued at 100%
to completion on day 14. This is another superb example showing both the
short-term and long-term benefits of LCD implementation.
Case 7 is a 48-year-old female T1D patient who
transferred to Takao Hospital for diabetes management and education to improve
glycemic control. Her HbA1c was 11.6%, GADA 1130 U/mL, and Glycoalbumin (GA)
was 24.2%. The insulin regimen on admission was 18 units of insulin glargine and
insulin lispro 4-2-2 units. The patient was given the super LCD containing
approximately 1600 kcal per day with 10 g of carbohydrates per meal (from
non-starchy plant foods). She was monitored with CGM for 7 days. Insulin requirement was quickly decreased,
and the regimen was revised to 10 units of insulin glargine and no Humalog by
discharge on day 7. As seen in Figure 2,
the calculated HbA1c was 6.5%. Glucose
briefly exceeded 200 mg/dL on the third day but improved afterward. TBR was 14% and 21% on days 1 and 2,
respectively but was 0% thereafter. This
patient achieved better glycemic control by injecting less insulin. Hypoglycemia
is avoided physiologically by gluconeogenesis and proper insulin dosing.
Case 8 is a 73-year-old female T1D patient who was
referred for inpatient evaluation and treatment of T1D for 7 days at Takao
Hospital. HbA1c and GA were 7.2% and
19.0?, respectively.
CPR and urine C-peptide were 0.2 ng/mL (1.5-3.5) and 16.6 ?g/day
(29.2-167), respectively, indicative of minimal endogenous insulin
secretion. The only agent used for
glucose lowering was insulin degludec scale 9-10 units depending on morning
FBG. The patient started a 1400 kcal per
day super LCD and was monitored with concurrent CGM. Data can be viewed in Figure 3.
The estimated HbA1c over 7 days was 5.9%, indicating
great improvement in glycemic control.
The glucose range was set from 80-160 mg/dL. TBR was calculated to be 7% over the 7 days. Glucose never dropped below 66 mg/dL and was
only below 70 mg/dL on 4 readings, however, the patient never complained of any
symptoms of hypoglycemia. Good glycemic
control was maintained on insulin degludec 9-10 units only. The patient was recommended to take miglitol
25mg only prior to carbohydrate intake upon discharge. This is another example of a simple and
effective medication regimen made possible by dietary modification.
Considerations
There
are growing data supporting the efficacy and safety of LCD. Conventional diets containing large amounts
of carbohydrate result in postprandial hyperglycemia and huge BG
fluctuations. LCDs prevent both postprandial
hyperglycemia and BG fluctuations that are seen in conventional diets. Avoiding postprandial hyperglycemia and BG
fluctuations, in addition to improvements in metabolic syndrome symptoms may
help prevent diabetic complications.
LCDs are also effective in decreasing insulin and OHA requirements in
diabetic patients with impaired endogenous insulin production. Many T1D and SPIDDM patients benefit from the
super LCD in both the short and long terms.
It appears that LCDs can prolong the Honeymoon period in T1D
patients. SPIDDM patients may eventually
progress to insulin dependence. However,
LCDs may slow progression in SPIDDM patients, as well. There is much more to learn in this regard,
and we hope to stimulate efforts to work out the details in the future.